Annual Report - GI Cancer64 GI Cancer Institute Sponsors RECOGNISING OUTSTANDING LEADERSHIP I am...

Annual Report

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The Australasian Gastro-Intestinal Trials Group (AGITG) and the GI Cancer Institute are dedicated to achieving better health outcomes for patients with GI cancer by conducting and promoting clinical and related biological research in Australasia and internationally, addressing key unanswered questions.

CONTENTS 2 The Year at a Glance5 About Us7 Our Global Presence8 Funding Gastro-Intestinal Cancer Research10 Chair’s Message12 Chief Executive Officer’s Report14 Group Coordinator’s Report16 Consumer Advisory Panel Report18 Clinical Trials21 Oesophageal Cancer22 Stomach Cancer, GIST & NETS24 Pancreatic, Gallbladder & Biliary Tract Cancer26 Colorectal & Anal Cancer31 Translational Research33 Journal Publications & Conference Presentations 36 Genesis of a Clinical Trial38 Annual Scientific Meeting42 Investing in Research48 Perpetual Grants Acquitted in 201750 Grants51 Organisational Structure52 Board of Directors56 Scientific Advisory Committee & Working Parties 59 Treasurer’s Report60 Income Statement61 Balance Sheet62 Your Support Makes the Difference64 GI Cancer Institute Sponsors

RECOGNISING OUTSTANDING LEADERSHIP I am deeply honoured to be a recipient of this award. To be thought of by my colleagues to have made a contribution to improving treatments for GI cancer I consider as high praise and I am most humbled to be recognised by this group of dedicated and determined medical practitioners.Professor Michael FindlayJohn Zalcberg OAM Award for Excellence in AGITG Clinical Trials Research

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• The first Australian patient is randomised to the InterAACT study in metastatic anal cancer from Austin Hospital

• An abstract from CommNETs about gastroenteropancreatic neuroendocrine tumours is an oral presentation at the American Society of Clinical Oncology Gastro-Intestinal Cancers Symposium, held in San Francisco

• A poster on the Engage Community Forums is presented at Survivorship Conference, by Consumer Advisory Panel members, held in Adelaide

• The ALaCaRT rectal surgery trial is selected by the American Society of Clinical Oncology for inclusion in Clinical Cancer Advances 2017

• The INTEGRATE clinical trial in gastro-oesophageal cancer is accepted into the Best of Journal edition of Clinical Oncology Gastrointestinal Cancer

• Sophia Hamblin Wang and friend Nik Wansbrough take on a 200km Gutsy Challenge run to raise funds for pancreatic cancer research in honour of her Aunty Helen

• The Consumer Advisory Panel and CEO make a submission to the Senate Select Committee into Funding for Research into Cancers with Low Survival Rates

• The Engage Community Forum with a focus on GI cancer research is held in Perth

• Catwalk for a Cause, a community event held in Perth, honouring Rosemary Fogliani who had stomach cancer, raises over $50,000 for stomach cancer research

• Olympian swimmers Cate and Bronte Campbell support AGITG member Dr Melissa Eastgate at a swim meet to raise funds for her Larapinta Gutsy Challenge

• Merck partners with the AGITG to offer the inaugural AGITG Clinical Research Fellowship to develop further collaboration between the AGITG and leading research institutes in the UK

• The AGITG Preceptorship in Upper GI Cancer supported by a Shire education grant and led by Professor Eva Segelov, a two day course for junior consultants and senior trainees, is held on the Gold Coast

• Results for the Advanced GIST trial for patients with unresectable or metastatic gastro-Intestinal stromal tumours is published in the Journal of Clinical Oncology

• The AGITG Consumer Advisory Panel and CEO present the AGITG submission to the Senate Select Committee into Funding for Research into Cancers with Low Survival Rates

• The AGITG Annual General Meeting held in Sydney coincides with open meetings of the Upper and Lower GI Working Parties

• AGITG clinical trial abstracts for ICECREAM (colorectal cancer), INTEGRATE II (gastro-oesophageal cancer) and SCOT (colorectal cancer) are presented at the American Society of Clinical Oncology Annual Meeting in Chicago

• The Neglected Cancers Awareness Week is held from 19-25 June to bring attention to rare and less common cancers with high mortality rates

• Turning his 50th birthday celebration into a fundraiser, Marcus Dawe raises close to $4,000 for pancreatic cancer to remember his Aunty Helen

• Katrina McNamara completes a 47km Gutsy Challenge swim raising funds for stomach cancer to honour her friend Marty Browne

• Dr Lorraine Chantrill, AGITG Director, and Adam Harvey, ABC reporter, join 15 other gutsy trekkers in the Larapinta Gutsy Challenge, raising funds for GI cancer research

• The AGITG trial TOPGEAR adding radiation to chemotherapy for re-sectable gastric cancer, led by Pro-fessor Trevor Leong, is published in the Annals of Surgical Oncology

• INTEGRATE, an AGITG designed and led trial using regorafenib in the treatment of stomach cancer, is published in Gastric Cancer Online

• Principal Investigator, Dr Mustafa Khasraw, presents a poster about the NABNEC trial for patients with Neuroendocrine Carcinomas (NEC) at the European Society for Medical Oncology

• AGITG Innovation Fund of $200,000 awarded to support the RENO study into rectal cancer

• 19th AGITG Annual Scientific Meeting held in Cairns

• The John Zalcberg OAM Award for Excellence in AGITG Clinical Trials is awarded to Professor Michael Findlay of Auckland Hospital

• Dr David Lau receives the inaugural Merck-AGITG Clinical Research Fellowship to be undertaken at The Royal Marsden Hospital in London

• The Best of New Concepts, supported by Specialised Therapeutics Australia, is awarded to Dr Katherine Geddes from St Vincents Hospital Melbourne

• Dr Jennifer Mooi is awarded the Best of Posters Award, supported by Ipsen

• Also supported by Ipsen, the Best Fast Forward presentation is awarded to Dr Melanie McCoy, who presents on behalf of Mr Tim Miller

• The AGITG Best Site Award is awarded to Orange Clinical Trials Centre for their outstanding work in establishing a pilot in tele-trials for rural centres

• The Living Room Series with Professor David Goldstein and Dr Chantrill focuses on pancreatic cancer to recognise Pancreatic Cancer Awareness Month

• Professor Goldstein is recognised at the NSW Premier's Award for Outstanding Cancer Research receiving the ‘Professor Rob Sutherland AO Make A Difference Award’

• The Sydney Opera House is lit up in purple to commemorate World Pancreatic Cancer Day

• Results for 2015 AGITG Innovation Fund are made available in gastric cancer and oesophageal cancer

• A/Professor Niall Tebbutt leads a group of intrepid trekkers climbing Mt Aconcagua to raise funds for GI cancer research

• Third annual CommNETs meeting held in Honolulu to improve outcomes for NET patients

• Final patient for ALT-GIST clinical trial is recruited

THE YEAR AT A GLANCE

FEB

JUN

APR

MARJAN MAY JUL

AUG

SEP

OCT NOV

DEC

2 3

54 clinical trialsimproving outcomes

for people with GI cancer

4,000+ patientsgiven access to new treatment regimens

on our trials

$52 million invested in AGITG

research

$

206 presentations based on AGITG trials

at global research conferences

1,177 peoplesupported through Engage Community

Forums

86 research articles by AGITG in peer reviewed

journals changing medical practice

ABOUT US

Since 1991, the key priority of the Australasian Gastro-Intestinal Trials Group (AGITG) has been to undertake research that is centred on patient care and improve medical practice in the treatment of GI cancer.

Our dedicated group of research and health professionals translate bold new ideas into clinical trials to defeat gastro-intestinal (GI) cancer, making GI cancer a manageable disease and ultimately a disease of the past. Our multi-disciplinary collaborative group of medical oncologists, surgeons, radiation oncologists, statisticians, data managers, allied health care professionals and

consumers focus on cancers of the oesophagus, stomach, liver, pancreas, gallbladder and biliary tract, large and small bowel, rectum and anus.

The GI Cancer Institute is the community division of the AGITG, working across Australia to raise funds and awareness of GI cancer and clinical trials. We are committed to changing the outcomes for people with GI cancer by finding cures and better treatments to improve their lives.

What are clinical trialsTreating GI cancers is often extremely complex requiring a combination of surgery, radiotherapy and specialist drugs (chemotherapy). To improve patient care clinical trials are needed

to evaluate which combination of treatments will work best for particular groups of tumours and people.

Clinical trials are not about laboratories and test tubes. They are about real people treating a disease with medications, surgical techniques and radiation treatments that need to be administered in the optimal combination to work best.

Conducting clinical trials in Australia means that Australian patients can access the latest treatments three to five years earlier than if the trials were conducted overseas. As a result of clinical trials major advances in treating GI cancers and improving patient quality of life are possible.

I became involved in the treatment of GI cancer over 20 years ago. There were not many treatment options available at the time for patients in Australia. I was fortunate to have a mentor who encouraged me in this area and since then I have witnessed exciting advances in care. I am honoured to be part of this positive change for patients with GI cancers.

Professor Tim Price Chair AGITG

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OUR GLOBAL PRESENCE

The AGITG plays a major role in clinical trial research on the global stage and has international collaboration links with the United Kingdom, Europe, Asia and North America.

�� Participating CentresClinical trials in recruitmentTOP GEAR, ASCOLT, CONTROL NETS, InterAACT, ACTICCA-1, NABNEC, INTEGRATE II

Clinical trials in follow-upDOCTOR, Advanced GIST, Adjuvant GIST, ALT-GIST, GAP, TACTIC, ATTACHE, ICECREAM, ALaCaRT, SCOT, CO.23, PETACC-6

�� Participating CentresClinical trials in recruitmentINTEGRATE II

Clinical trials in follow-up ALT-GIST

�� Participating CentresClinical trials in recruitmentTOPGEAR, INTEGRATE II

�� Participating CentresClinical trials in recruitmentTOP GEAR

Clinical trials in follow-up ICECREAM, ALT-GIST

� Participating CentresClinical trials in recruitmentTOPGEAR, ASCOLT, INTEGRATE II

Clinical trials in follow-upPETACC-6, ALaCaRT, SCOT

� Participating CentresClinical trials in follow-upICECREAM, ALT-GIST

� Participating CentresClinical trials in recruitmentINTEGRATE II

Canada UK

USA Asia

Australia NZ

Europe

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As part of my medical practice, every day, I see families affected by pancreatic cancer. I have been participating in clinical trials to find a better way to treat my patients and to honour a promise I have made to those I have treated to do whatever I can to improve the life expectancy for people with pancreatic cancer.

Dr Lorraine Chantrill

Australia

Asia New Zealand

Canada UK

Europe USA

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1

24

5

3

6 7

8

9

RESEARCH IS CRUCIAL TO IMPROVING SURVIVAL RATES

�. OESOPHAGUS

��.�%� year survival rate

�. LARGE BOWEL


�. PANCREAS

�.�%� year survival rate

�. LIVER


�. RECTUM

��%� year survival rate

�. STOMACH


�. ANUS


�. SMALL BOWEL


�. GALL BLADDER


Help us lift the survivalrate of

GI cancer

GIcancer

Breastcancer

Prostatecancer

49%

92%90%

FundingGastro-Intestinal Cancer Research

MORE FUNDING MEANS BETTER SURVIVAL RATESIn Australia breast and prostate cancer are two of the highest incidence cancers and have witnessed steady progress in treatment and improved survival. These two cancer types now have < 20% annual mortality and > 90% 5 year survival rates because of significant research funding.

Research funding for colon & rectum cancer, cancers of the pancreas, oesophagus and stomach is low compared with their burden on the Australian population.* *Cancer Research in Australia 2016 to 2018 Opportunities for strategic research investment

24,600 Australiansare diagnosed every year

with GI cancer

33 Australians die every day of the year

as a result of GI cancer

33

1 person dies every 45 minutes

from GI cancer

8 9

I am pleased to report that in 2017 we made significant progress in achieving our Mission to conduct and promote clinical and related biological research in Australia and addressing key unanswered questions in GI cancer research.

As an organisation we have invested heavily in the past year to develop a remarkable number of new innovative trials to open to patient participation in 2018, adding considerable value to our clinical trials portfolio.

Notably, we have seen the development of two Innovation Fund grants awarded in 2016 and 2017. One, the MONARCC Study, is a randomised phase II trial of panitumumab monotherapy and panitumumab plus 5-fluorouracil as first line therapy for RAS and BRAF wild type metastatic colorectal cancer, led by Chief Investigator Dr Matthew Burge. And the other is the RENO Study, Prospective Study of ‘Watch and Wait’ Strategy in Patients with Rectal Cancer who have Developed a Clinical Complete Response with concurrent Chemo-radiotherapy (REctal cancer No Operation), led by Chief Investigator Professor Chris Karapetis. These studies will produce results which will impact the treatment of patients with advanced colorectal and localised rectal cancers. This outcome for our Innovation Fund grants demonstrates the value of our rigorous scientific process and the AGITG clinical trial pipeline, from identification of patient need to improving treatments for people with GI cancers.

In recent years there have been exciting new developments taking place in the area of personalised medicine, analysis and targeting treatment in many cancers. We are making progress in this area

for GI cancers. There were several trials under development in 2017: DYNAMIC Pancreas, DYNAMIC Rectal and DYNAMIC III (colon cancer). Led by Associate Professor Peter Gibbs and Associate Professor Jeanne Tie, the DYNAMIC clinical trials involve analysis of circulating Tumour DNA (liquid biopsies) informing adjuvant chemotherapy treatment in early stage pancreatic cancer, locally advanced rectal cancer and stage III colon cancer. In addition, the LIBERATE Study, led by Associate Professor Niall Tebbutt, will evaluate liquid biopsies to profile metastatic colorectal cancer.

Other trials that have been developed in 2017 include the SPAR Study, a randomised, placebo-controlled phase II trial of simvastatin in addition to standard chemotherapy and radiation in preoperative treatment for rectal cancer, led by Chief Investigators Associate Professor Michael Jameson and Professor Stephen Ackland. The MODULATE Study examines modulation of the tumour microenvironment using either vascular disrupting agents or STAT3 inhibition in order to synergise with PD1 inhibition in microsatellite stable, refractory colorectal cancer, led by Chief Investigator Associate Professor Niall Tebbutt.

An important piece in the development of our clinical trials pipeline is the ongoing commitment of the AGITG to encourage and support the next generation of early career researchers. In 2017, the inaugural Merck-AGITG Clinical Research Fellowship in Gastro-Intestinal Cancer was awarded to Dr David Lau from the Olivia Newton-John Cancer Research Institute. The fellowship is based at The Royal Marsden Hospital, London and the overall objective of the Research Fellowship is to increase collaboration between the UK and Australia.

Of organisational note, in 2017 the AGITG launched a new website. This was necessary after in-depth consultations with stakeholders determined that the organisation’s communication objectives required a fresh approach. The new site presents information relevant to both our clinical and community audiences. Please visit the site at www.gicancer.org.au.

There are so many dedicated individuals contributing to the success of our organisation. I was honoured to present the John Zalcberg OAM Award for Excellence in AGITG Clinical Trials Research to Professor Michael Findlay. The Award recognises a member of the AGITG who has made significant and outstanding leadership contributions to AGITG clinical trials research over a sustained period. He was a founding member of the AGITG, participating back in the ‘90’s in the initial discussions around improved care for people with gastro-intestinal cancer, when the group was a loose network of investigators. Professor Findlay is well known for his patient-centred focus in clinical trial research.

It is not possible to list the names of the numerous people in both the AGITG and GI Cancer Institute community who have contributed in many ways to improving and saving the lives of patients with GI cancer. From the countless voluntary hours spent on research, to climbing mountains in Argentina and trekking through the Northern Territory, we must acknowledge the enormous effort made by innumerable people to address the key unanswered questions in achieving better health outcomes for patients and their families with gastro-intestinal cancer.

Professor Tim PriceMBBS DHthSc (Med) FRACP Chair

CHAIR’S MESSAGEIn 2017, the dedicated network of health professionals that make up the membership of the Australasian Gastro-intestinal Trials Group (AGITG) continued facing challenges and scaling mountains, both literally and metaphorically, to improve outcomes for people with gastro-intestinal cancer.

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There was a notable shift in 2017 in the zeitgeist around awareness and support for cancers with low survival rates. Three of the eight cancers with the highest mortality rates (> 70%) are cancers of the liver, pancreas and oesophagus, whilst six of the twelve cancers with the lowest five year survival rates (< 30%) are also gastro-intestinal cancers – pancreas, liver, gallbladder and biliary tract, oesophagus, stomach and other digestive organs. This shift in our community augurs well for the future development of clinical trials and research into better treatments for patients with gastro-intestinal (GI) cancer.

Over the course of the year, there were several significant public events indicating a turning point for these diseases; in particular, the establishment of a Senate Select Committee into Funding for Research into Cancers with Low Survival Rates, chaired by Senator Catryna Bilyk. I was pleased to work with the Consumer Advisory Panel to develop a submission to the Senate Committee which resulted in an invitation to appear as witnesses at a Senate Committee hearing, to provide more information about low survival rate gastro-intestinal cancers.

Of further note, the Federal Minister for Health, The Hon Greg Hunt MP, announced that the Medical Research Future Fund will provide targeted funding for research into rare cancers, which bodes well for patients with gastro-intestinal cancers such as those mentioned above.

In 2017 the AGITG developed several new clinical trials for rare cancers including the DYNAMIC Studies in pancreatic cancer and rectal cancer, both investigating the use of liquid biopsies (circulating tumour DNA) to help identify more targeted treatment options for patients; and the SPAR Study investigating preoperative treatment for rectal cancer.

Colorectal cancer is not rare. In fact it is estimated that in 2017 there were 16,682 people diagnosed with the disease in Australia, making it the second highest in incidence, after breast cancer (17,730 cases) and just ahead of prostate cancer (16,665 cases). With a five year survival rate of just 69%, colorectal cancer compares poorly against breast cancer (90%) and prostate cancer (95%).

This past year several colorectal cancer clinical trials were developed by the AGITG, including Innovation Fund grant recipient - the MONARCC Study for metastatic colorectal cancer in an underserved older patient population; the LIBERATE Study, which will investigate liquid biopsies as a method of evaluating RAS mutation status in patients with advanced colorectal cancer; the DYNAMIC-III Study for Stage III colon cancer exploring treatment according to circulating tumour DNA results; and the MODULATE Study for patients with refractory colorectal cancer.

In an exciting development for patients in rural and remote areas, the AGITG launched a pilot of a new and innovative tele-trial model in 2017 whereby patients can be treated at satellite centres closer to home than the larger centres that participate in clinical trials. In 2015, the National Health Performance Survey revealed that a third of people in western New South Wales, country Western Australia and

country areas in South Australia believed that they had to wait too long to see a doctor. For cancer patients, especially those eligible for clinical trials, this lack of access can limit treatment options. The ASCOLT clinical trial for colorectal cancer was chosen for the tele-trial pilot with Dr Rob Zielinski at Orange Clinical Trials Centre treating trial patients receiving treatment via tele-link at Dubbo Base Hospital.

For over 25 years, members of the AGITG have recognised the need to focus on research and increase funding opportunities for better outcomes for patients with GI cancers. To this end, in 2017, the AGITG Board of Directors and management undertook an extensive strategic review to better position the organisation to take advantage of the changing climate and to accelerate the pace of discovery in gastro-intestinal cancer.

Three key themes for focus emerged:

1) Improve capacity and capability to develop and conduct research;

2) Improve and maintain engagement across the disciplines to drive development and conduct of multidisciplinary research; and

3) Improve organisation cost-effectiveness to drive sustainability.

These themes are reflected in a renewed Strategic Plan that was approved in late 2017 and which will be implemented over the coming five years. Central to the strategy is investment in pilot research to generate data to support funding submissions for large-scale practice changing research. The community arm of the AGITG, the GI Cancer Institute, has been charged with increasing charitable funding to

CHIEF EXECUTIVE OFFICER’S REPORT

support AGITG pilot study grants awarded through the AGITG Innovation Fund. Receiving an AGITG Innovation Fund grant is a result of having undertaken an extensive development process along the AGITG research development pathway. This pathway includes: identification of priority research areas by the AGITG Scientific Advisory Committee; development of embryonic new ideas into research concepts at the New Concepts Symposium; and assessment and refinement of research concepts by the AGITG Upper and Lower GI Working Parties. The final step is review and comment from the AGITG Consumer Advisory Panel to ensure the research meets the needs of the community. This framework ensures that our community-based charitable revenue is distributed to projects that have undergone rigorous scientific and consumer review processes.

Of course, this research is only possible with considerable funding support. Last year a major success for the GI Cancer Institute’s Gutsy Challenge community fundraising program was achieved. For the first time, two separate challenges were pursued, both involving AGITG Board members. On one, Dr Lorraine Chantrill led sixteen fellow hikers on the Larapinta Trail in the Northern Territory. On the other, Associate Professor Niall Tebbutt led a group of eight intrepid mountaineers up 6,962-metre high Mt Aconcagua in Argentina, the tallest peak in South America. Together, the two inspiring endeavours raised a record total of over $250,000 in support of the AGITG Innovation Fund.

The community is rallying. There is a discernible shift toward a focus on underfunded cancers, resulting in a growing sense of optimism in our medical community for advancing the treatment of gastro-intestinal cancer. None of this

is possible without the support of our community of medical professionals, patients, families, survivors, carers, donors and supporters. With your continued support we will harness the momentum to further improve the lives of people with gastro-intestinal cancer and their loved ones.

Russell Conley FIML MFIA Chief Executive Officer

Pictured (Top L-R):1. Mr Russell Conley, CEO, welcoming participants

to the Annual Scientific Meeting (ASM)2. Associate Professor Niall Tebbutt, Ms Brie

Jelbart and Mr Jason Long training for Mt Aconcagua climb

3. Dr Matt Burge presenting at the ASM4. Larrapinta trekkers heading out for one of the

2017 Gutsy Challenges5. Professor Michael Findlay (centre) accepting

his award from Professor Tim Price (left) and Professor John Zalcberg OAM (right)

6. AGITG Annual Scientific Meeting held in Cairns

12 13

I am pleased to report the Australasian Gastro-Intestinal Trials Group continues to undertake significant clinical trials research, leading to major new findings and helping to improve clinical practice in Australia, New Zealand and worldwide. Since its inception some 26 years ago, AGITG has undertaken 54 clinical trials in collaboration with international groups in Australia, New Zealand, Asia, Europe, the UK and North America and recruited over 4,000 participants.

2017 was marked by significant progress on some major international trials (particularly in gastric cancer and GIST tumours), with important new publications and reports and the development and funding of trials expected to open in 2018.

The TOPGEAR trial evaluating the addition of chemoradiotherapy to neoadjuvant chemotherapy prior to surgery for the management of gastric cancer showed that this combined regimen could be safely delivered without significant excess toxicity. These interim results published this year have helped spearhead the recruitment of the international phase III trial (with 388 of a planned 620 patients in total) to assess the impact of this treatment on overall survival.

The phase II INTEGRATE trial of a biologic therapy in gastric cancer (regorafinib) has shown a significantly longer time to cancer progression or worsening quality of life compared with best supportive care for patients with advanced disease. This has led to our international phase III trial (INTEGRATE II) in Australia, NZ, North America and Asia with initial 42 patients recruited and most remaining countries expected to join during 2018.

Despite some challenges in recruitment to the ALT-GIST trial evaluating a novel alternating adjuvant treatment for patients with GIST tumours, we are pleased that this international trial was able to reach its revised target of 78 patients and close to recruitment at the end of 2017. The trial has been led by AGITG in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC) and the Scandinavian Sarcoma Group (SSG). Patients will be followed for at least 18 months and the final study results are expected in 2019. Other trials with ongoing recruitment in 2017 include the assessment of aspirin to prevent colorectal cancer recurrence (ASCOLT), and the use of radioisotope therapy (CONTROL-NETS) and new chemotherapy regimens (NABNEC) to treat neuroendocrine tumours. We are pleased to have been awarded additional funding in August from the Unicorn Foundation to support the conduct of the CONTROL-NETS trial.

A number of new trials have been funded and are recently underway or about to commence recruitment. The MONARCC Study, evaluating panitumumab monotherapy compared with panitumumab plus 5-fluorouracil as first line therapy for RAS and BRAF wild type metastatic colorectal cancer, was awarded an AGITG Innovation Grant in 2016 with additional support from Amgen providing both additional funding and supply of panitumumab. Led by Mathew Burge, the trial aims to recruit older patients (70+ years) to assess the effect of treatment on the cancer, quality of life and levels of activity. The SPAR Study is evaluating the use of simvastatin when added to chemoradiotherapy to surgery for rectal cancer. This trial has been awarded grant funding from Cancer Council NSW and Cancer Australia in addition to earlier support in New Zealand from the NZ Cancer Society. Michael Jameson,

based in New Zealand, and Steve Ackland in Australia are co-leading this collaborative effort. The RENO Study, a prospective study of ‘Watch and Wait’ Strategy in Patients with Rectal Cancer who have Developed a Clinical Complete Response with concurrent Chemo-radiotherapy, led by Chris Karapetis, was the recipient of the 2017 Innovation Fund and will open to recruitment in 2018. These three studies are also important ones in that they are each addressing identified gaps in treatment of colorectal and rectal cancer.

Other trials that have been developed in 2017 in collaboration with the AGITG include: the DYNAMIC trials (in pancreatic, rectal and colon cancer), led by Jeanne Tie and Peter Gibbs. These trials, recruiting from 2018 will focus on circulating tumour DNA analysis to inform strategies for modifying chemotherapy according to the ctDNA results in individual patients. In addition, the LIBERATE study, led by Niall Tebbutt will evaluate liquid biopsies to profile metastatic colorectal cancer and the MODULATE study, also led by Niall Tebbutt will assess whether modulation of the tumour microenvironment using either vascular disrupting agents or STAT3 inhibition might synergise treatment with PD1 inhibition in microsatellite stable, refractory colorectal cancer.

The ASCOLT study, Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers, continues to recruit in ANZ and internationally to evaluate the use of aspirin to prevent recurrence of colorectal cancer with the planned 1200 patients near to completion. This trial has recently been used to pilot a tele-trial to assess making such trials accessible to more patients in distant locations. Led by Orange Hospital, it will pilot a new clinical trial model that will increase accessibility to this and potentially future trials, to more regional and rural patients. If this approach

GROUP COORDINATOR’S REPORT

proves feasible and it will give an opportunity to extend this model to other settings in future trials.

We received funding from the National Health & Medical Research Council (NHMRC) for two translational research projects: DOCTOR: Improving oesophageal adenocarcinoma outcomes through understanding genomics and treatment toxicity, and ASCOLT: Personalisation of Aspirin Adjuvant Therapy in Patients with Colorectal Cancer. Both of these projects involve laboratory based research with blood and/or tissue samples from study participants and the correlation of those results with clinical outcome data from the relevant trial.

There have been five peer reviewed manuscript publications in 2017 and 12 presentations at the European Society for Medical Oncology (ESMO), American Society of Clinical Oncology Annual Meeting (ASCO), and American Society of Clinical Oncology Gastro-Intestinal' Cancers Symposium (ASCO-GI).

During 2017, much work was undertaken in preparing new concepts and grant applications thanks to the diligence of several people within the AGITG in collaboration with the NHMRC Clinical Trials Centre and through the AGITG Upper and Lower GI Working Parties.

The collaboration of many people on a global basis continues to underpin the

efforts of our clinical trials research program. The hard work of clinical investigators, research coordinators and staff at each site, at the AGITG, the NHMRC Clinical Trials Centre, and all the AGITG committee members, have contributed significantly to the successful outcome of this research. We are indebted to the patients and their carers for their support and the vital services they bring to these trials.

Professor John SimesMD MBBS BSc SM FRACP Group Coordinator

Pictured: Professor Stephen Ackland, member Scientific Advisory Committee with Mr Grant Baker, member Consumer Advisory Panel

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In 2017, after the retirement of several members, the year commenced with a review of Expressions of Interest to join the Panel.

We welcomed five new members – Gillian Worden (QLD), Autumn Tansey (VIC), Grant Baker (NSW), Jeff Cuff (NSW) and Brian Wall (WA). We now have representation from all mainland states with upper GI cancer and lower GI cancer represented, and a mix of patients and carers. The Annual General Meeting in May gave everyone the opportunity to meet and attend the Upper and Lower GI Working Parties open meeting.

Following this meeting, the Panel elected to submit posters for the AGITG Annual Scientific Meeting. After thoroughly researching content, two topics were selected: Optimum Care Pathways and Mobile Health Care Apps. Both poster proposals were accepted by the Meeting Executive Committee and were presented at the meeting. It is hoped to submit these posters at other scientific events in the future.

In 2017 the CAP reviewed three AGITG clinical trial concepts including DYNAMIC-III, DYNAMIC-Rectal and DYNAMIC-Pancreas studies. Lay summaries of results of the CO.23, SCOT and Advanced GIST studies were reviewed by the Panel prior to posting on the web site.

A highlight for 2017 was the submission from the AGITG to the Senate Select Committee into Funding for Research into Cancers with Low Survival Rates. Following this submission, we were asked to present as witnesses and provide more details to the Committee. The CEO Russell Conley, Dan Kent, Professor John Simes and myself attended and Julie Marker (SA) and James Armstrong (VIC) participated

by tele-link. We outlined the difficulties of identification and funding for research into the GI cancers that currently present with low survival.

2017 saw increases in knowledge of immunotherapy, diversity in left and right sidedness in colorectal cancer, ongoing challenges due to the increase in genomic knowledge and additional data on diet, biome and exercise. This knowledge and these challenges will make up the trial landscape in 2018. The Consumer Advisory Panel will continue to support these endeavours as well as the key activities of new trial review, identification of gaps, patient information and consent and recruitment strategies. Members of the Panel are present on the Upper and Lower GI Working Parties and Expressions of Interest are sought for other committees as needed.

The AGITG Consumer Advisory Panel provides a voice and perspective of people, carers, and families and survivors impacted by GI cancer.

The Consumer Advisory Panel also supports the GI Cancer Institute with community outreach initiatives by participating as speakers and supporting fundraising through programs such as the Gutsy Challenge.

Jan Mumford Chair Consumer Advisory Panel

Pictured (L-R): Mr Brian Wall, Ms Autumn Tansey, Ms Christine BIshop, Ms Julie Marker, Ms Gillian Worden, Mr Grant Baker, Mr Jeff Cuff, Ms Jan Mumford, Mr Robin Mitchell. Not in photo – Mr James Armstrong

CONSUMER ADVISORY PANEL REPORTThe AGITG Consumer Advisory Panel are responsible for the review of new trial concepts; identifying gaps in research; assisting with the ease of understanding of trial patient information and consent forms; and advising on patient recruitment strategies.

James’ StoryJames Armstrong’s father, Australian artist Ian Armstrong, was first diagnosed with bowel cancer in 1970. Ian went through two bowel resections and survived for 35 years past his initial diagnosis, before passing away in 2005 from a recurrence of rectal tumours and heart disease.

After witnessing his father’s experience, James knew that he had to monitor his health, and he began having colonoscopies in 2001. Nine years later, in 2010, James remembers, “My worst nightmare came true”. A pre-cancerous polyp was detected in his results. James underwent an anterior bowel resection.

Since then, James has been a committed advocate for health promotion, disease prevention and public health. As a member of the AGITG’s Consumer Advisory Panel he advises on clinical trials from a consumer perspective. In 2017 he ran 10km for Run Melbourne to raise awareness and funds for GI cancer research. He has also completed a Master of Public Health at Monash University.

“I’m really passionate about the importance of clinical trials and their benefits,” says James. “I think it’s paramount that we raise awareness about the benefits of clinical trials and how important they are in the fight against cancer.”

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Clinical Trials

CLINICAL TRIALS MAKE A DIFFERENCE AGITG clinical trials have contributed significantly to the improvement of outcomes for people with GI cancer.

These positive outcomes can be seen in the improvements in five year survival rates.*Source AIHW 2012 - Series 69, Cat no CAN 65**Source: AIHW 2017 Cancer Series Number 101

I am very grateful for the generosity of donors who provided the necessary funds for the AGITG Innovation Grant to begin the pre-planned and very exciting DOCTOR genomic substudy. The grant funded DNA copy number analyses that were performed on tumour tissues from participants providing important insights in oesophageal tumour biology and serving as important first steps for subsequent next generation sequencing studies.

Professor Andrew Barbour

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Oesophageal cancer in Australia continues to grow at an alarming rate. In 2011, there were 1,395 new diagnoses, and in 2017 there were 1,642 diagnoses. In 2017, it claimed 1,418 lives. The five year survival rate is only at 20.1%.

Trials open to recruitmentINTEGRATE II Following the promising results from the INTEGRATE study, INTEGRATE II, an AGITG led Phase III clinical trial in gastro-oesophageal cancer, is open to patient participation in Australia, New Zealand, Korea, Canada, and Taiwan. The first patient on the study was recruited late in October 2016 at Townsville Hospital, QLD. Since that time, 26 sites have opened throughout Australia and New Zealand, recruiting 23 patients, 12 sites in Korea, recruiting 23 patients, nine sites in Canada, recruiting one

patient, and two sites in Taiwan. Ten sites in the US are expected to open in 2018, with seven sites expected to open in Japan in the first half of 2019.

There are currently few effective treatment options for patients with Advanced Gastro-Oesophageal Cancer (AGOC) that has returned after surgery, or where it is metastatic at diagnosis. Chemotherapy can be effective at first, but once the cancer has become resistant to it, the options for treatment are limited. For those who do receive additional courses of chemotherapy, their cancer will eventually become resistant (or ‘refractory’) to these drugs. In these situations, there are currently no accepted treatment options that have been shown to be both effective against the cancer and tolerable for patients. Better treatment options are urgently needed.

Regorafenib (BAY 73-4506) is a ‘multi-targeted therapy’ targeting a number of different signals in the cancer cell that cause it to grow and produce blood vessels. In other cancers, such as colon cancer and GIST, regorafenib has been proven to be of benefit when other drugs have ceased to work. The earlier AGITG Phase II trial, INTEGRATE, demonstrated efficacy with the use of regorafenib in AGOC, and could potentially become a new standard of care after other therapeutic agents have stopped working. INTEGRATE II is being undertaken to confirm the findings of the Phase II trial in a larger population. If the study is positive it will provide evidence for regorafenib as a new standard of care after other treatments no longer benefit patients with stomach cancer, also known as gastric cancer.

Trials in follow-upDOCTORThis study broke new ground in pre-operative therapy for oesophageal cancer. It was the first to focus on changing the therapy for metabolic non-responders to pre-operative therapy to try to improve response and, potentially, survival. It was also innovative in other ways, such as assessing whether changing therapy can salvage a response. It provided valuable data regarding the potential to individualise therapy related to the tumour characteristics – so-called ‘tailored therapy’. Surgery forms the mainstay of curative treatment – but survival remains poor. Pre-operative chemotherapy, with or without concurrent radiotherapy, has resulted in modest improvements in outcome. Increasing the proportion of responders to pre-operative therapy remains one of the major challenges facing patients with localised oesophageal cancer. Recruitment of patients ended on 31 December 2015.

The primary analysis was presented at the 2016 Congress of the European Society of Medical Oncology (ESMO). Docetaxel added to chemotherapy and particularly with radiotherapy can induce high rates of histological responses in non-metabolic responder patients. Therefore, tailoring multimodality therapy based on individual PET response is safe and feasible in oesophageal cancer, although the impact on survival requires longer follow-up.

CLINICAL TRIALS: OESOPHAGEAL CANCER Clinical Trials

It is very exciting to be involved with such a great research team in developing and leading an international Phase II and now Phase III trial, for patients with advanced gastric cancer. We hope that at the conclusion of the INTEGRATE II trial, we will have definitive results on the use of regorafenib to extend people’s lives with this cancer.

Associate Professor Nick Pavlakis

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Although stomach cancer is on the decline in Australia, it still affects a significant number of people. In 2011, 2,093 Australians were diagnosed with the disease and 1,143 people died in 2012. In 2017 incidence of stomach cancer increased to 2,294; however, fewer people, 1,084, died in 2017 than in 2012. The five-year survival rate is now at 28.5%.Trials in recruitmentTOPGEARFor patients with stomach cancer, surgery may cure those with localised cancer, but most patients present with more advanced cancer. When treated with surgery, it will recur in 70% of patients.

Thus, surgery alone is not an adequate treatment. There are

currently two ‘standard’ methods used worldwide to treat patients whose stomach cancer is more advanced – either treatment with chemotherapy before and after surgery, or a combination of radiation plus chemotherapy following surgery.

We believe that combining these two approaches will provide even greater benefit, especially if the combination of radiation plus chemotherapy is given prior to surgery.

This randomised controlled trial will build on previous research conducted and compare chemotherapy given before and after surgery, with or without adding concurrent chemotherapy and radiotherapy. The trial is being led by Australian investigators and includes participation by groups in Australia, Canada and Europe.

TOPGEAR is currently in phase III with 388 patients enrolled as of 31 December 2017. An amendment to the protocol was made in June 2017 to reduce the target total sample size from 752 to 620 and to allow the addition of FLOT and EOX as standard chemotherapy regimens for patients on trial. A formal analysis is due to take place in the first or second quarter of 2018 (after 300 patients have been followed up for a minimum of 6 months from completion of adjuvant chemotherapy), which will include testing for efficacy (progression free survival) and futility. Preparation for this analysis has begun, including review of criteria. Part I, Phase II results were published in Annals of Surgical Oncology in March 2017.

CONTROL NETsNeuroendocrine tumours (NETs) are rare cancers that can develop in different locations throughout the body, including the gastro-intestinal tract and the pancreas. These cancers develop from neuroendocrine cells. These cells are usually found in the nervous system and the endocrine (hormone) system, and help to control normal body functions. NETs

that have spread around the body (metastasised), or can’t be removed by surgery are incurable using currently available treatments. Some patients can survive for long periods, depending on the growth rate of the cancer cells. Although NETs are rare in terms of the number of new cases per year, the total number of patients with NETs in Australia at any given time builds up, impacting on the community.

The aim of the study is to assess whether the combination of radiopeptide and chemotherapy is more effective than either radiopeptide or chemotherapy alone in mid-gut and pancreatic NETs. If the combination treatment demonstrates a more positive effect, this could then be further investigated in a larger phase III randomised trial, the results of which would guide best practice.

The study has now recruited 65 out of 75 patients. Although CONTROL NETs was unsuccessful in receiving a grant from the NHMRC in 2017, the study has been supported by additional funds from the Unicorn Foundation received in August 2017.

NABNECThe aim of the study is to assess if a carboplatin and nab-paclitaxel chemotherapy combination is an effective and tolerable treatment for advanced Neuroendocrine Carcinomas (NECs). The trial will also look at outcomes of survival, monitor the side effects of treatment, identify useful markers of prognosis and response, and increase our understanding of the biology of NECs.

NABNEC was funded by an NHMRC Project Grant from 2016-2020 and ethics approval was obtained in March 2016. Seventeen sites have been selected. Additional payment per patient and supply of nab-paclitaxel was provided by Specialised Therapeutics Australia and executed in August 2016. Since the study opened in 2016, 14 patients have been recruited to the trial. A poster was presented at

CLINICAL TRIALS: STOMACH CANCER, GIST & NETS

the European Society for Medical Oncology (ESMO) meeting in 2017 and has been accepted for a poster presentation at the American Society for Clinical Oncology GI (ASCO-GI) meeting in 2018.

Trials in follow-upALT-GIST Gastro-intestinal stromal tumours (GIST) are rare cancers that can develop in different locations throughout the gastro-intestinal tract. When they have spread to other places (metastasised) or are not able to be surgically removed, they are not curable with any current treatment.

Medications have been developed that improve survival in patients with metastatic GIST. They work by blocking the signals that make these cells grow and spread. One of two drugs available on the Pharmaceutical Benefits Scheme in Australia, imatinib is used as the initial treatment for incurable GIST. Although many people with metastatic disease respond to imatinib initially, in almost all cases the cancer eventually becomes resistant to this drug and starts to grow. Until recently, a search for active new medicines in this setting had failed, but since then, regorafenib was shown to significantly delay progression in this setting. Regorafenib works in a similar way to imatinib although it targets a number of additional enzymes in tumour cells. This may explain its activity when imatinib is no longer active. There are 37 sites participating across Australia, Asia, Europe and Scandinavia with 78 patients recruited at the end of December 2017. Recruitment of patients to the trial is now closed.

Trials completed EORTC 62005 – Advanced GISTThe Advanced GIST trial was conducted in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC). It compares higher and lower doses of imatinib to see which works best.

This trial was opened to recruitment in 2001 and has had a number of papers published. The interim analysis for this trial was printed in 2005, and at that time if not resectable or if metastatic, were judged to be untreatable. The interim analysis indicated that initial treatment with imatinib 400mg twice a day induces significantly longer progression-free survival compared with treatment once a day. The benefit in terms of median progression-free survival was an extra 5 months. This benefit suggested 400mg imatinib twice a day as preferred dose when duration of effect is crucial, such as in metastatic disease with symptoms. During 2016/2017 analysis of the long term follow-up data was undertaken. Eleven publications have resulted from this trial to date. The EORTC and AGITG agreed to cease follow-up in September 2016 with more than 10 years of follow-up data collected. In 2017, results were published in the Journal of Clinical Oncology.

EORTC 62024 – Adjuvant GISTThe Adjuvant GIST trial, also conducted with the EORTC, aims to determine if giving imatinib to people with early-stage GIST as a follow-up treatment after surgery increases their survival rate. After 2 years of treatment and a median follow-up of 4.7 years, the interim analysis of the data confirmed that adjuvant imatinib has an overt impact on Relapse Free Survival. No significant difference in imatinib monotherapy failure-free survival was observed, although in the high-risk subgroup there was a trend in favour of the adjuvant arm. Results of the interim analysis were printed in the Journal of Clinical Oncology in October, 2015.

Data collection and follow-up of these patients was completed in December 2016 when data cleaning and the final analysis for this trial was undertaken. These results were presented at ESMO 2017 and published in Annals of Oncology.

Clinical Trials

Sophia and Nik’s StoryWhen Sophia Hamblin Wang’s Aunty Helen was diagnosed with pancreatic cancer in August 2016, she remembers being overwhelmed with helplessness and anger.

“I thought it was totally unfair that she was dealt such a cruel blow,” says Sophia.

Pancreatic cancer has a five-year survival rate of just 7.7%. Helen’s cancer was deemed inoperable, as is the case for many patients.

“My family tried to get Helen enrolled in a clinical trial but the majority of the applicable ones were overseas,” says Sophia.

Sophia decided to take on a Gutsy Challenge, joined by her friend Nik Wansborough, whose uncle-in-law lost his life to stomach cancer in 2016. Together they ran 200km and raised over $4,000 for GI cancer research.

“I feel strongly that we need more research in Australia,” says Sophia. “By supporting the GI Cancer Institute, we can do our part to help more Australians engage in the medical research ecosystem, and potentially access revolutionary treatments.”

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Clinical Trials

Pancreatic cancer is amongst the most lethal of all adult cancers and growing – 3,271 people were diagnosed with pancreatic cancer in 2017 and an estimated 2,915 people died from it in Australia in 2017. The five year survival rate is just 7.7%. There have been no major improvements in outcomes over the last 30 years.

Trials in activationDYNAMIC Pancreas DYNAMIC Pancreas is a circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Early Stage Pancreatic Cancer.

In the majority of cases, long term survival can only be achieved with surgical removal of localised disease but despite ‘curative intent’ surgery, 80-85% of patients relapse. Clinical trials have shown

that chemotherapy after surgery may provide some benefit. The use of a single drug treatment with gemcitabine or fluoropyrimidine was accepted as standard of care. However, results from a recent trial in patients with advanced pancreatic cancer demonstrated a significant improvement in overall survival when patients were treated with a combination therapy (that is, gemcitabine plus capecitabine vs gemcitabine alone). This may translate into greater benefits for patients with localised pancreatic cancer. However, it remains difficult to adequately measure risk and treatment effectiveness for all patients.

The aim of this study is to demonstrate that a ctDNA informed approach to chemotherapy, following surgery for localised pancreatic cancer, could lead to a reduction in the proportion of patients with detectable ctDNA after completion of treatment compared to standard of care. Recruitment for patients will open in 2018.

GAPThis trial aims to evaluate the impact that pre-operative pancreatic cancer chemotherapy has in increasing the quality of the surgery to remove the cancer. For surgery in pancreatic cancer to be considered successful there must be no cancer left over after surgery, but this is often hard to achieve due to the way the cancer grows into vital structures. It will also assess treatment-related toxicity and treatment failure.

Recent research suggests that the combination of gemcitabine and Abraxane (nab-paclitaxel) brings significant improvement in response and overall survival in the metastatic setting. Therapy before surgery is able to identify patients with aggressive tumour biology, who may be spared the effects of resection surgery, while

also identifying patients most likely to benefit from radical therapy.The analysis undertaken concluded that pre-operative gemcitabine and nab-paclitaxel is feasible and well tolerated.The pre-operative regimen was associated with an RO resection rate comparable or higher than surgical series without pre-operative therapy, although the primary endpoint of 85% could not be met. The value of this regimen will also depend on longer term outcomes related to recurrence and survival. The GAP study had a poster presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting, as well as the ASCO GI Meeting, in 2015. Another presentation was held in 2016 at the ASCO Annual Meeting.

Cancer of the gallbladder and bile ducts is rare, accounting for 902 people diagnosed in 2017 and 261 deaths in 2017. The five year survival rate is only at 19.2%.

Trials open to recruitmentACTICCA-1Cholangiocarcinoma is a type of cancer that develops in the bile ducts. Bile ducts are tubes that drain bile, a fluid produced in the liver, into the gut to help with the digestion of food. This type of cancer is rare, with only a few hundred cases in Australia every year. It occurs more often as people get older. There are still many unanswered questions about the best way to treat this cancer. If the cancer is only in the bile ducts, and has not spread to other parts of the body, the best treatment is to remove all the cancer with surgery. Unfortunately, even though surgery is sometimes possible, the cancer can come back in many people. For some other types of cancer, giving extra treatment with chemotherapy after surgery has been useful. However, there is no definitive trial evidence at the moment to show

if this is true for cholangiocarcinoma. There is a need for a comparison study to help improve the survival for people with this cancer.

This trial will help us to know if giving a chemotherapy combination of cisplatin and gemcitabine after surgery is better than standard of care treatment (capecitabine chemotherapy since 2017) after surgery for cholangiocarcinoma in non-metastatic patients. It will monitor people to see how often their cancer comes back, and see if this happens less often when the combination chemotherapy is used. It will also monitor the side effects from the treatment, quality of life and complications from surgery, amongst other things. This trial initially

opened to recruitment in Australia in July 2016 and initially compared the combination of chemotherapy with cisplatin and gemcitabine after surgery to observation only after surgery. In 2017, results from another clinical trial demonstrated that treating patients with capecitabine delays recurrence of their cancer. This chemotherapy treatment has been adopted as standard of care since then. Therefore, the ACTICCA-1 clinical trial was temporarily stopped and the aim was adjusted to compare the ACTICCA-1 study treatment to the new standard of care treatment with capecitabine. The trial reopened to recruitment in November 2017. As of 31 December 2017 five Australian sites have opened and 10 additional sites are expected to open in 2018.

CLINICAL TRIALS: PANCREATIC, GALLBLADDER & BILIARY TRACT CANCER

Pictured Above: Associate Professor Peter Gibbs, Principal Investigator, DYNAMIC PancreasPictured Below: Dr Jenny Shannon, Principal Investigator, ACTICCA-1 chairing a session at the Annual Scientific Meeting

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Colorectal cancer is cancer of the colon or rectum. It is also called bowel cancer and is the most common type of GI cancer. Australia has one of the highest rates of colorectal cancer in the world. In 2017, 16,682 people were diagnosed with colorectal cancer and 4,114 died in Australia. The five year survival rate is now at 68.7%.

Trials in activationSPARThis randomised phase II trial aims to evaluate the effect of simvastatin (SIM) on efficacy and toxicity of preoperative chemoradiotherapy in rectal cancer patients, and on systemic and local inflammatory responses.

Rectal cancer is often treated by chemotherapy and radiation before surgery, but if the cancer responds poorly to this treatment many patients relapse. Retrospective studies show better cancer responses and fewer side effects in patients taking a statin drug (for cholesterol) during radiation therapy. This study will recruit 222 patients from hospitals in Australia and New Zealand to test if taking a statin for 3 months (during combined chemotherapy and radiation then for another 6 weeks) improves the rate of good tumour response and reduces side effects of this treatment.

Recruitment for patients will open in the first quarter of 2018.

MONARCCThe aim of this study is to investigate the activity of treatment with the anti-EGFR therapy panitumumab alone and panitumumab combined with 5-fluorouracil chemotherapy, in a molecularly selected, elderly patient population with metastatic colorectal cancer.

Metastatic colorectal cancer is a disease of the elderly. Anti-EGFR antibodies have not been well studied in an elderly patient population unsuited to combination chemotherapy. The median age in trials involving these agents is 60-65 years. As a result there is an opportunity to investigate the activity of anti-EGFR monotherapy, or combined with “light” chemotherapy in a molecularly selected, hitherto under-investigated but prevalent patient population.

Recruitment for patients will open in Australian sites in the first quarter of 2018.

LIBERATE LIBERATE is a study evaluating liquid biopsies to profile metastatic colorectal cancer. The purpose of this study is to investigate liquid biopsies as a method of evaluating

RAS mutation status in patients with advanced colorectal cancer. This involves determining the accuracy of results of liquid biopsies, compared to genetic testing of cancer tissue. Different methods of testing liquid biopsies will be studied and compared. The study will also assess whether the ability of liquid biopsies to detect cancer gene mutations is different at different time points.

This study will compare the results of liquid biopsies with results from traditional genetic testing of cancer tissue, in order to validate liquid biopsies as an acceptable method of evaluating RAS mutation status.

Recruitment for patients will open in 2018.

DYNAMIC-RectalThe DYNAMIC-Rectal trial is a multicentre randomised study of Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Locally Advanced Rectal Cancer.

Colorectal cancer (CRC) remains a major health burden in Western countries and is rapidly increasing in incidence elsewhere where Western lifestyles are being adopted. Approximately 30% of colorectal cancers arise within the rectum, where pre-operative chemo-radiation (CRT) and then surgery is standard for patients with locally advanced rectal cancer (LARC). While multiple advances have been made in managing rectal cancer, patient selection for adjuvant chemotherapy after surgery, and agent choice remain major clinical dilemmas.

The aim of this trial is to demonstrate that a chemotherapy decision incorporating ctDNA results in addition to standard pathologic risk assessment will reduce the number of patients receiving adjuvant chemotherapy.


DYNAMIC-IIIDYNAMIC-III is a Multi-centre Phase II/III Randomised Controlled Study of Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Stage III Colon Cancer.

Currently, the standard treatment for stage III colon cancer is surgical removal of the tumour followed by 3-6 months of chemotherapy. Chemotherapy is given as a combination treatment made up of 3 drugs including oxaliplatin or as a single drug treatment with fluoropyrimidine. Although studies have shown that chemotherapy reduces the risk of the cancer returning, not all patients benefit from treatment. For some, the cancer is cured by surgery alone, and others will experience cancer relapse even with treatment. It is difficult to adequately measure risk and treatment effectiveness for all patients.

The aim of this study is to demonstrate that a chemotherapy decision based on the presence or absence of circulating tumour DNA after surgery will be more effective than standard of care treatment, as measured by how many patients remain cancer free at 3 years.


RENORENO is a prospective study of ‘Watch and Wait’ Strategy in Patients with Rectal Cancer who have Developed a Clinical Complete Response with concurrent Chemo-radiotherapy.

Rectal cancer is a common malignancy and comprises a third of the cases of colorectal cancer. Currently, a combination of chemotherapy plus radiotherapy followed by surgical resection of the rectum is the standard management of locally advanced rectal cancer. Approximately 20% of patients

develop a pathological complete response to chemoradiation. In these patients, surgery may not be necessary. There are retrospective studies showing the safety of a watch and wait strategy instead of surgery in patients who do not have any signs of disease after completing chemoradiation. This approach may save the patient from surgical risks and long-term morbidity.

With this study, the aim will be to assess the safety of the watch and wait approach in this population and prove the feasibility of a structured follow-up program. The study will also assess novel biomarkers, patient reported outcome measures and health economics; none of which have been studied in this population.

Recruitment of patients will be open in 2018.

MODULATETME MODULATE is a study of the modulation of the tumour microenvironment using either vascular disrupting agents or STAT3 inhibition in order to synergise with PD1 inhibition in microsatellite stable, refractory colorectal cancer.

The MODULATE trial aims to test whether it is possible to enable lymphocytes to enter bowel cancer tumours, and to attack them once they are inside. Researchers will recruit 90 patients at 15 sites across Australia. Everyone who joins the trial will have advanced bowel cancer, and will have exhausted all standard treatments. This trial provides them with the option of trying an experimental treatment which may prove to have an effect.

Both of these approaches are experimental as they have not been tested on people with bowel cancer before. Researchers hope that one of the approaches will be effective in shrinking tumours.

Recruitment of patients will be open in 2018.

Trials open to recruitment ASCOLTAspirin is known to be helpful in preventing and treating heart and blood vessel diseases. There is growing evidence that aspirin also has some anticancer properties. Studies that have looked at large groups of patients with colorectal cancer suggest that aspirin might be able to reduce recurrence of the cancer and improve survival in patients with localised colorectal cancer. However, these findings need to be confirmed by information from randomised clinical trials before treatment with aspirin can be considered standard therapy for this group of patients. Investigating the role of aspirin in colorectal cancer patients was chosen as the highest priority by Australian consumers, clinicians and researchers at a national forum convened by the AGITG and University of Sydney in August 2011.The ASCOLT study will provide proof of the role of aspirin in patients with localised colorectal cancer and will set a new standard nationally and internationally. As aspirin is inexpensive, readily available and familiar to most people, any impact on increased survival is likely to result in it being widely used as a cost effective agent.

ASCOLT is being conducted in 12 countries throughout Asia, Australia and New Zealand.

A successful Cancer Australia grant application was submitted in March 2016 and a second Cancer Australia grant was awarded in January 2017. AGITG will be the lead for overall translational activities in collaboration with the Walter and Eliza Hall Institute. As of 31 December 2017, the trial has recruited 267 patients with up to 36 sites in Australia and New Zealand.

CLINICAL TRIALS: COLORECTAL & ANAL CANCER Clinical Trials

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ASCOLT Tele-TrialRural patients experience difficulties in accessing clinical trials closer to home mainly because of the limited number of available clinical trial sites in rural and regional areas. Additionally, studies have shown that long distance travel and expenses associated with travel are barriers to uptake of trials by rural and regional patients. Given that many cancer centres use teleoncology models to provide oncology services including chemotherapy services in rural areas, these models offer an opportunity to improve rural access to clinical trials.

One such model is a Tele-trial model. This model allows oncologists from established cancer centres to establish consent, recruit and manage patients on trials in rural and regional towns. The ASCOLT study will be run as a tele-trial with Orange Hospital as primary site and Dubbo Hospital as secondary site.

Trials in follow-upInterAACTThe main purpose of this international, multicentre trial is to establish which chemotherapy regimen is more effective for inoperable advanced or metastatic anal cancer. By comparing two well-known and widely used combination chemotherapies, researchers aim to demonstrate which one is more effective and less toxic for patients with this disease. The results of this study are likely to establish the standard of care for patients with inoperable anal cancer. This study also aims to acquire important information on the biology of anal cancer by incorporating translational research as part of its overall research aim.

The first site was open to recruitment in March 2016. Since then an additional four sites have opened and three patients in Australia have been recruited.

The trial closed to recruitment in 2017.

ICECREAMPrevious AGITG studies have demonstrated that cetuximab, an epidermal growth factor receptor (EGFR) monoclonal antibody, prolongs survival in patients refractory to all other chemotherapy, which has resulted in Australian Pharmaceutical Benefits Scheme funding (in September 2011). Some doctors believe combining this treatment with irinotecan will achieve better results because one older UK trial reported modest increases in cancer shrinkage and duration of cancer control. However, side-effects were found to be greater and survival was not increased on this study.

Soon after the initial cetuximab clinical trials were reported, the AGITG and other groups showed that cetuximab was not effective in people who have a specific abnormality (mutation) in their colon cancer cells called a KRAS Gene Mutation. Up to 40% of patients have this abnormality, which can be easily tested, and so only patients without this mutation (KRAS wild-type) are given this treatment. When restricted to this subgroup, the benefits of the cetuximab are significantly enhanced.

The picture has become more complicated, as further research has been presented showing that patients with one particular type of KRAS mutation (G13D) may actually benefit from cetuximab treatment after all. Currently, however, cetuximab is only US FDA and Australian TGA approved for patients without any KRAS mutation.

This study aims to evaluate whether cetuximab should be given alone or in combination with irinotecan chemotherapy in KRAS wild-type patients with progressing cancer despite previous treatment with oxaliplatin and irinotecan

chemotherapy. The aim is to evaluate whether this approach has beneficial effects in patients with the specific G13D KRAS mutation.

Recruitment closed on 30 June 2016 with the final total recruitment of 101 patients. In 2016, analysis was published in the Journal of Clinical Oncology and an abstract of was presented at ASCO 2017.

ALaCaRTALaCaRT is the largest Australasian trial in rectal surgery. The current major treatment for rectal cancer is surgical removal of the cancer, requiring a large cut through the abdomen. The ALaCaRT trial looks at whether a less invasive laparoscopic resection is as safe and effective as the current procedure.

This trial was not testing whether the new treatment was better, but rather whether it was no worse than the traditional treatment. Therefore, it was a non-inferiority trial. The outcome was not clear-cut. The trial showed that non-inferiority was not ruled out. That is, open surgery could be better. The tumour was completely or almost completely removed in 97% of the laparoscopic surgery group and 99% of the open surgery group. The margin around the tumour was completely clear in 93% of patients in the laparoscopic group and 97% of those having open surgery. Results of this trial were published in the Journal of the American Medical Association in 2015. The ALaCaRT rectal surgery trial was selected by the American Society of Clinical Oncology for inclusion in Clinical Cancer Advances 2017, the society’s annual review of progress against cancer and emerging trends in the field. Follow-up continues with a publication on two-year survival and disease recurrence results expected in 2018.

SCOTFor patients who have had surgery to remove all of their bowel cancer,

the SCOT trial will determine if 12 weeks of chemotherapy treatment is as effective as, and less toxic than, 24 weeks. If successful, the SCOT trial will significantly minimise short- and long-term side-effects of chemotherapy and will decrease the financial burden of treatment.

The SCOT trial is coordinated internationally by the Cancer Clinical Trials Unit Scotland (CaCTUS) and the Oncology Clinical Trials Office (OCTO) at the University of Oxford.

Main analysis of the study is underway with the aim of publishing the first SCOT results in mid-2018. In addition to this an analysis of the toxicity and quality of life data is also planned, with the aim of publication in 2018.

Trials completedPETACC-6An international study led by the European Organisation for the Research and Treatment of Cancer (EORTC), PETACC-6 is testing whether adding the new chemotherapy drug oxaliplatin to standard chemotherapy and radiotherapy before and after surgery improves disease-free survival for people with locally advanced rectal cancer. The PETACC-6 database was locked on 31st December 2015 and analysis of data was undertaken early in 2016. The results were presented at ESMO 2016 as a poster presentation. Five year follow-up data was collected until mid-June 2017 followed by data cleaning. The analysis is currently underway.

CLINICAL TRIALS: COLORECTAL & ANAL CANCER Clinical Trials

Pictured Above: Dr Amitesh Roy, Principal Investigator, InterAACT Pictured Below: Professor Eva Segelov, Principal Investigator, ICECREAM

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Tissue and blood samples collected from AGITG trial patients are an important part of the research. These samples are used in translational research studies to seek biomarkers, biological flags that may help to select those patients most likely to benefit from a treatment, or to spare particular patients from treatment toxicities.

Thirty-six AGITG trials currently collect or have collected tissue and blood from patients. Over 80% of these trials have confirmed translational research studies using these samples. Work is progressing on many of these studies. Translational research proposals undergo scientific review by the trial management committees, the upper and lower GI working groups and the Scientific Advisory Committee (SAC).

Proposals relating to the GI trial collaborations between AGITG and the Canadian Clinical Trials Group (CCTG) are reviewed by the joint AGITG-CCTG Correlative Research Committee several times a year. There are currently fifteen translational research studies underway using biospecimens from three colorectal cancer trials (CO.17, CO.20 and CO.23) and another two correlative studies relating to biological parameters such as age of patient. Our research collaborators are with a broad mix of clinical and scientific researchers from Australia, New Zealand, and overseas.

2017 highlights include • The rectal cancer trial, SPAR,

was awarded a project grant funding from Cancer Australia and will collect tissue samples from patients for a range of translational research studies.

• Our Australian-led trials are collecting patient tissue and blood samples across an unprecedented number of countries:

– ALT-GIST a trial in gastro-intestinal stromal tumour (GIST) has patient samples collected from 8 countries: Australia, Belgium, France, Finland, Slovakia, UK, Sweden and Singapore.

– TOPGEAR a trial in gastric cancer, is collecting patient samples from 10 countries: Australia, Belgium, Canada, Czech Republic, France, Germany, Israel, New Zealand, Slovenia and Spain.

• A correlative study about age of patients with colorectal cancer treated with targeted therapies was presented as a poster at the American Society of Clinical Oncology Annual Meeting in Chicago1 by Canadian collaborator, Conner Wells. It looked at data from two colorectal cancer trials (CO.17 and CO.20). From the CO.17 trial, being 70 years or older in age was neither prognostic nor did it predict how well a patient would respond to treatment with cetuximab. In contrast, the second trial showed that these older patients had a worse prognosis. The researchers also reported that although elderly patients who participate in clinical trials of a targeted therapy may get similar survival benefits as younger patients, they may not derive the same improvement in their quality of life.

1. Connor Wells, Lillian L. Siu, Jeremy David Shapiro, Dongsheng Tu, Derek J. Jonker, Christos Stelios Karapetis, John Simes, Geoffrey Liu, Timothy Jay Price, Niall C. Tebbutt, Christopher J. O'Callaghan. Age as a predictive and prognostic factor for targeted therapy treatment in metastatic chemorefractory colorectal cancer (CRC): An analysis of NCIC CTG CO.17 and CO.20. Journal of Clinical Oncology 35, no. 15_suppl (2017) 3555-3555.

TRANSLATIONAL RESEARCH

Adam’s StoryABC journalist Adam Harvey’s training for the GI Cancer Institute’s Larapinta trek was on track until he was shot on assignment in the Philippines. Instead of slowing down, Adam recovered and then continued training. He completed the five-day trek less than six months after being wounded.

Adam had a personal motivation for committing to the fundraising challenge. In 2012, his father, Peter Harvey, was diagnosed with pancreatic cancer, and Adam knew that the disease was probably terminal. His wife’s stepfather, Ian Carroll, had also lost his life due to pancreatic cancer. Peter Harvey died just three months after his diagnosis.

“It’s a disease that desperately needs more research,” says Adam. “With only a 7.7% survival rate for pancreatic cancer, a focused and determined effort is needed to improve the outcomes for those diagnosed.”

By taking on the 80km trek, Adam successfully raised over $9,000 to fund research that will improve treatment methods and life expectancy for people diagnosed with gastro-intestinal cancers.

“To help the next generation of Peter Harveys and Ian Carrolls, more research is needed – and that, of course, means more money.”

Stomach cancer remains a significant global public health problem; worldwide it is still a leading cause of cancer-related deaths. TOPGEAR could change clinical practice worldwide and we are now collecting patient tissue and blood samples across a number of countries for future testing through the TOPGEAR trial.

Professor Trevor Leong

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Journal publications and conference presentations provide clinicians and patients with the most up-to-date treatment results. In 2017, the AGITG published clinical trial results in leading international medical journals. The five publications included trials in advanced gastric cancer, gastro-intestinal stromal tumours, locally advanced rectal and pancreatic cancer.

Publications EORTC 62005Ten-year progression-free and overall survival in patients with unresectable or metastatic GI stromal tumors: long-term analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastro-Intestinal Trials Group intergroup phase III randomized trial on imatinib at two dose levels. Casali PG, Zalcberg J, Le Cesne A, Reichardt P, Blay JY, Lindner LH, Judson IR, Schoffski P, Leyvraz S, Italiano A, Grunwald V, Pousa AL, Kotasek D, Sleijfer S, Kerst JM, Rutkowski P, Fumagalli E, Hogendoorn P, Litiere S, Marreaud S, van der Graaf W, Gronchi A, Verweij J. Journal of Clinical Oncology 2017; 35(15): 1713–1720.

TOPGEARA randomized, phase III trial of perioperative ECF chemotherapy with or without preoperative chemoradiation for resectable gastric cancer: interim results from an international, intergroup trial of the AGITG, TROG, EORTC and CCTG. Leong T, Smithers BM, Haustermans K, Michael M, Gebski V, Miller D, Zalcberg J, Boussioutas A, Findlay M, O'Connell RL, Verghis J, Willis D, Kron T, Crain M, Murray WK, Lordick F, Swallow C, Darling G, Simes J, Wong R. Annals of Surgical Oncology 2017; 24(8): 2252–2258.

INTEGRATE Health-related quality of life associated with regorafenib treatment in refractory advanced gastric adenocarcinoma. Martin AJ, Gibbs E, Sjoquist K, Pavlakis N, Simes J, Price T, Shannon J, Gill S, Jain V, Liu G, Kannourakis G, Kim YH, Kim JW, Goldstein D. Gastric Cancer. Online 18 Aug 2017.

Current challenges in optimizing systemic therapy for patients with pancreatic cancer: expert perspectives from the Australasian Gastro-Intestinal Trials Group (AGITG) with invited international faculty. Segelov E, Lordick F, Goldstein D, Chantrill LA, Croagh D, Lawrence B, Arnold D, Chau I, Obermannova R, Price TJ. Expert Review of Anticancer Therapy 2017; 17(10): 951–964.

Evaluating the addition of oxaliplatin to single agent fluoropyrimidine in the treatment of locally advanced rectal cancer: a systematic review and meta-analysis. Thavaneswaran S, Kok PS, Price T. Expert Review of Anticancer Therapy 2017; 17(10) 965–979.

PresentationsIn 2017, members of the AGITG presented at international cancer conferences in the US and Europe. Showcasing AGITG trial results to international colleagues is an important focus for the AGITG at these high profile international conferences. Results for INTEGRATE, INTEGRATE II, MAX, NABNEC, IMPACT, SCOT, ICECREAM, EORTC 62024 and ARCAD were featured.

European Society for Medical Oncology 42nd Congress, MadridEORTC 62024Time to definitive failure to the first tyrosine kinase inhibitor in localized gastro-intestinal stromal tumors treated with imatinib as an adjuvant: final results of the EORTC STBSG, AGITG, UNICANCER, FSG, ISG, and GEIS randomized trial. Casali PG, Le Cesne A, Poveda A, Kotasek

D, Rutkowski P, Hohenberger P, Fumagalli E, Judson I, Italiano A, Gelderblom H, Penel N, Kopp HG, Goldstein D, Martin Broto J, Gronchi A, Wardelmann E, Marreaud S, Zalcberg J, Litière S, Blay JY.

SCOTUpdated results of the SCOT study: an international phase III randomised (1:1) non-inferiority trial comparing 3 versus 6 months of oxaliplatin based adjuvant chemotherapy for colorectal cancer. Iveson T, Kerr R, Saunders M, Hollander NH, Tabernero J, Haydon A, Glimelius B, Harkin A, Scudder C, K. B, Waterston A, Medley LC, Wilson C, Ellis R, Essapen S, Dhadda A, Harrison M, Falk S, Abdel-Raouf S, Paul J.

NABNECA randomised phase II study of nab-paclitaxel in combination with carboplatin as first line treatment of gastro-intestinal neuroendocrine carcinomas. Khasraw M, Hofman MS, Chantrill L, Pavlakis N, Gebski V, Gill AJ, Markman B, Yip S, Gibbs E, Karapetis C, Wong SF, Ransom DT, Michael M, Wilson K, Simes J, Lipton L.

MAX Consensus molecular subtypes as predictors of benefit from bevacizumab in first line treatment of metastatic colorectal cancer: retrospective analysis of the MAX clinical trial. Mooi J, Wirapati P, Asher R, Lee C, Savas P, Price T, Tejpar S, Mariadason J, Tebbutt N.

INTEGRATE Accuracy and prognostic significance of oncologists estimates and scenarios for survival time in a randomised phase 2 trial of regorafenib in advanced gastric cancer. Vasista A, Martin A, Pavlakis N, Sjoquist K, Snow S, Jonker D, Chua YJ, Epstein R, Bonaventura A, Khasraw M, Varma SC, Singhal N, Ransom D, Aubin F, Burkes RL, Lim H, Lemay F, Begbie S, Stockler M, Kiely B.

JOURNAL PUBLICATIONS & CONFERENCE PRESENTATIONS

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American Society of Clinical Oncology 2017 Annual Meeting, ChicagoSCOTFinal DFS results of the SCOT study: an international phase III randomised (1:1) non-inferiority trial comparing 3 versus 6 months of oxaliplatin based adjuvant chemotherapy for colorectal cancer. Iveson T, Kerr R, Saunders MP, Hollander NH, Tabernero J, Haydon AM, Glimelius B, Harkin A, Scudder C, Boyd K, Waterston AM, Medley LC, Wilson C, Ellis R, Essapen S, Dhadda AD, Harrison M, Falk S, Raouf S, Paul J.

ICECREAMResults of the quad wild-type arm of the AGITG ICECREAM study: a randomised phase II study of cetuximab alone or in combination with irinotecan in patients with refractory metastatic colorectal cancer with no mutations in KRAS, NRAS, BRAF or PIK3CA. Shapiro JD, Thavaneswaran S, Underhill C, Robledo KP, Karapetis CS, Day FL, Nott LM, M. J, Chantrill LA, Pavlakis N, Tebbutt NC, Price TJ, Khasraw M, Van Hazel G, Waring PM, Tejpar S, Simes J, Gebski V, Desai J, Segelov E.

SCOTProspective pooled analysis of six phase III trials investigating duration of adjuvant (adjuv) oxaliplatin-based therapy (3 vs 6 months) for patients (pts) with stage III colon cancer (CC): The IDEA (International Duration Evaluation of Adjuvant chemotherapy) collaboration. Shi Q, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, Sougklakos I, Kerr R, Labianca R, Meyerhardt JA, Bonnetain F, Watanabe T, Boukovinas I, Renfro LA, Grothey A, Niedzwiecki D, Torri V, Andre T, Sargent DJ, Iveson T.

INTEGRATE IIA randomised phase 3 double-blind placebo-controlled study of regorafenib in refractory advanced gastro-oesophageal cancer—an international study organized by the Australasian Gastro-Intestinal Trials Group. Sjoquist KM, Pavlakis N, Martin AJ, Tsobanis E, Yip S, Bang YJ, Alcindor T, O'Callaghan CJ, Shitara K, Bekaii-Saab TS, Grothey A, Chen LT, Simes J, Zalcberg R, Goldstein D.

American Society of Clinical Oncology Gastrointestinal Cancers Symposium, San FranciscoARCADTumor-size-based endpoints as surrogates for overall survival in the ARCAD advanced colorectal cancer database. Burzykowski T, Coart E, Saad ED, Sargent D, Zalcberg J, Shi Q, Sommeijer DW, Buyse ME.

IMPACTClinical utilization of targetable molecular results in pancreatic cancer: longer-term outcomes from the Individualized Molecular Pancreatic Cancer Therapy (IMPACT) trial. Chantrill LA, Nagrial A, Johns A, McKay S, Gill AJ, Pavlakis N, Grimison PS, Asghari G, Waddell N, Chou A, Chin VT, Sebastian LT, Verghis J, Yip S, Sjoquist KM, Simes J, Biankin A.

Retrospective cohort analysis of neoadjuvant treatment and survival in resectable and borderline resectable pancreatic ductal adenocarcinoma in a high-volume referral centre. Itchins M, Arena S, Rabindran J, Christopher N, Kim S, Gibbs E, Gill AJ, Maher R, Schembri G, Bailey E, Mittal A, S. B, Wong M, Hruby G, Kneebone A, Pavlakis N, Samra JS, Clarke S.

JOURNAL PUBLICATIONS & CONFERENCE PRESENTATIONS

David's StoryAt 68, David McInnes still felt very much in his prime. He ran a printing business and regularly ran between 160 and 200km a week, travelling around the world to compete in marathons. He enjoyed spending time with his partner, sons and grandson.

Out of the blue, he began to feel sharp pains in his left side as he lay down to sleep. He became extremely fatigued. After being admitted to hospital for tests, he was diagnosed with stage 4 neuroendocrine cancer.

Neuroendocrine tumours (NETs) are rare. They occur in parts of the gastro-intestinal system as well as the endocrine system, which regulates the body’s hormones.

David underwent surgery to remove a mass in his stomach as well as 57 lymph nodes. He was able to participate in the AGITG’s CONTROL NETS trial, which is the first trial where a range of treatment options for NETs patients have been tested against each other. David was randomly allocated radiotherapy treatment, and four months later received promising news.

“When a doctor tells you your results aren’t just positive, but better than before, that gives you a lift,” he says. “It’s an upward journey, not a downward journey.”

It is a great honour for me to lead the RENO Study with the recognition and support that the AGITG Innovation Fund Grant provides. I anticipate that our study will guide clinical practice and I hope that findings will lead to a clinical meaningful improvement for patients with Rectal cancer.

Professor Chris Karapetis

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STEP 2.Discussions with colleagues

Recognising the needs of his patient, Professor Karapetis held a number of discussions with his medical colleagues, including surgeons, radiologists and other colleagues at Flinders Medical Centre in Adelaide to discuss a watch and wait approach.

STEP �. Literature reviewA search for information to guide the treatment management of this approach identified a few small studies but did not confirm a watch and wait evidence-based treatment path. There was a distinct gap in knowledge.

STEP �. Recognition that there was no clear treatment guidance on ‘watch and wait’ approach

Professor Karapetis recognised the need to develop a Watch and Wait protocol based on evidence. He then took the next step and put together a proposal of a concept for a study, titled “Prospective Study of Watch and Wait Strategy in Patients with REctal Cancer who have Obtained a Clinical Complete Response with concurrent Chemo-radiotherapy: RENO trial (Rectal cancer No Operation)”.

STEP �. Presentation to local and international peersProfessor Karapetis decided the best way forward was to get formal feedback from AGITG members and international speakers attending the AGITG Annual Scientific Meeting, and he submitted the study concept into the 2016 New Concepts Symposium. The concept was popular and the audience responded positively. The proposed study was recognised as of important scientific interest with several meeting participants indicating they would contribute to the study if it were to be opened by the AGITG.

STEP �. Further development and presentationIn collaboration with surgical colleagues in Adelaide, Professor Karapetis continued to work on the study plan. This plan was then presented to the AGITG Lower GI Working Party and the concept was also reviewed by the AGITG Scientific Advisory Committee. The AGITG’s Upper GI and Lower GI Working Parties are the working parties of the Scientific Advisory Committee (SAC). The working parties include medical oncologists, surgeons, radiation oncologists, statisticians, translational scientists, consumers and allied health practitioners. The Lower GI Working Party looks at cancer of the bowel, anus and rectum while the Upper GI Working Party focuses on cancers of the oesophagus, gallbladder, pancreas, stomach and liver.

STEP �. How to fund the study?Professor Karapetis submitted the study proposal to the NHMRC for funding but unfortunately was unsuccessful. In 2017, he then made the decision to apply for the AGITG Innovation Fund for a grant to conduct the RENO clinical trial pilot.

STEP �. Application to AGITG Innovation Fund

Professor Karapetis prepared a grant application for the 2017 AGITG Innovation Fund and was awarded a $200,000 grant. The AGITG Innovation Fund is made possible by the generosity of donors.

STEP �.A clinical trial is startedThe clinical trial to provide pilot evidence for this treatment approach will be open to recruitment in 2018 with funding from the AGITG Innovation Fund, ten years after Professor Karapetis’s rectal cancer patient came to him wanting to watch and wait before further treatment.

To successfully obtain funding for academic research and the establishment of a clinical trial takes a considerable amount of effort, time and collaboration across multi-disciplinary teams. Follow the genesis of an AGITG clinical trial, RENO (REctal cancer No Operation) from identification of the problem to obtaining funding for a study supported by the AGITG Innovation Fund.

Rectal cancer is a common malignancy and comprises one third of the cases of colorectal cancer

diagnosed in Australia. Currently, a combination of chemotherapy plus radiotherapy followed by surgical resection of the rectum is the standard management of locally advanced rectal cancer. Approximately 20% of patients develop a pathological complete response to chemo-radiation. In these patients, surgery may not be necessary. The aim of this study is to assess the safety of the watch and wait approach in this population and to prove the feasibility of a structured follow-up program. The study will also assess novel biomarkers, patient reported outcome measures and health economics, none of which have been studied in this population before.

STEP �. Identification of a gap in researchTen years ago, Professor Chris Karapetis, a medical oncologist, was treating a young patient with rectal cancer. This patient had a good response to chemotherapy and did not want surgery due to long-term risks and the possibility of surgery resulting in a stoma. He insisted on watching and waiting.

GENESIS OF A CLINICAL TRIAL

Pictured: Professor Tim Price congratulating Professor Chris Karapetis on receiving the 2017 Innovation Fund Award

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ANNUAL SCIENTIFIC MEETING

Under the guidance of Professor Eva Segelov, Meeting Convenor, and the Annual Scientific Meeting (ASM) Executive Organising Committee, the AGITG Meeting continued to provide a forum for mutual exchange of knowledge to improve the treatment of patients with gastro-intestinal cancer.

Our invited speakers from across the globe represented a distinguished group of experts from multi-disciplinary fields. We were privileged to host:

Associate Professor Thierry AlcindorMedical Oncologist, McGill University, Canada (representing AGITG Collaborative Partner the Canadian Cancer Trials Group)

Professor John BridgewaterMedical Oncologist, UCL Cancer Institute, UKDr Ian Chau Medical Oncologist, Royal Marsden Hospital, UKProfessor Karyn Goodman Radiation Oncologist, University of Colorado, USAProfessor John V. Reynolds Surgeon, St James Hospital and Trinity College, IrelandProfessor Sean GrimmondPathologist, University of Melbourne/Victorian Comprehensive Cancer Centre, Australia

A Keynote Breakfast Session sponsored by Merck started the first day. In the pursuit of precision treatment of colorectal cancer, biomarker discovery has had a major impact on selection of therapy. However biomarkers and consensus molecular subtypes still fail to fully inform treatment decisions. Sidedness of primary tumour has emerged as an additional and potent factor in identifying which therapy

should be offered to which patient. Dr Ian Chau explored data related to confirmed and potential biomarkers, impact of consensus molecular subtypes on therapy, and the role of tumour sidedness and other clinical features in aiding the practising clinician choose the best possible treatment for their patient.

The AGITG Opening Plenary, sponsored by the Meeting Platinum Sponsor Amgen Australia, which featured three esteemed speakers: Professor Sean Grimmond, Professor John Bridgewater and Professor John Simes presenting a forward looking view of the major issues confronting clinicians and patients with gastro-intestinal cancer in the modern era. Presentations focussed on personalised medicine, why recent advances in other cancers have not been replicated in GI cancer and how to design trials and therapies to be more effective.

Following the Opening Plenary was the Translational Science Symposium, also sponsored by Amgen Australia and co-chaired by Professor Bridget Robinson and Dr Jayesh Desai. We were delighted to have four prominent national speakers who are focussed on translational research across a range of GI cancers, including neuroendocrine tumours, pancreatic cancer and colorectal carcinoma. This continues the recent AGITG ASM tradition of exploring how we can both develop bench-science into clinical trials, as well as explore how cutting edge translational platforms in Australia can help address key translational questions in locally-led, AGITG trials. Exciting new developments presented included

“What you see ain’t what you NET” by Dr Ben Lawrence; “New Translational approaches and technologies: optimal use for maximal benefit” Professor Sean Grimmond; “The promise of ctDNA in GI cancer – from screening to advanced disease” by Associate Professor Peter Gibbs; and “Somatic Mutations, Infiltrative

Immune Cells and Prognosis in DNA Mismatch Repair Deficient Subtypes of Colorectal Cancer” by Dr Dan Buchanan.

The Study Coordinators Forum provided an overview of oesophagogastric cancer with an emphasis on the use of new targeted therapies in a changing clinical trial environment and the impact these new treatments have on overall quality of life.

The New Concepts Symposium sponsored by Specialised Therapeutics Australia was held at the end of Day One. The Symposium is designed as a novel way to reach out to a wider spectrum of the AGITG membership.

AGITG trials were presented in sessions across the three days:

• Colorectal and Anal Cancer Trials including updates on ICECREAM, SCOT, ASCOLT, InterAACT, CO.23 and plans for our newest trials MONARCC, SPAR, and LIBERATE.

• Oesophagogastric trial updates included TOPGEAR, DOCTOR and INTEGRATE II.

• The Hepatobiliary, GIST and NET trial session included presentations on ALT-GIST, ACTICCA-1, NABNEC, CONTROL NETS and NABCAPABIL.

Day Two of the conference was held in collaboration with the Australia & New Zealand Gastro Oesophageal Surgery Association (ANZGOSA), an association for surgeons to provide a vehicle for improving the surgical management of diseases of the stomach, oesophagus and upper gastro-intestinal tract.

The day started with a Keynote Breakfast. Professor Reynolds presented on “Obesity, Diabetes and Oesophageal Adenocarcinoma: Lessons from the Bench and the Bedside.”

The theme for the Plenary – “One swallow does not a summer make:

This year, a tropical setting provided the back drop for delegates from around Australia, New Zealand and further afield to get down to business at the 19th

Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting held in Cairns, Queensland on 4-6 October.

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Associate Professor Andrew Kneebone with Professor Karyn Goodman leading a Radiation Oncology Contouring Workshop. We were honoured to host Professor Goodman who is a prominent member of the Radiation Therapy Oncology Group (RTOG) GI community and regularly chairs RTOG GI contouring workshops.

The Best of the Best/Fast Forward session was sponsored by Ipsen. The AGITG Annual Scientific Meeting accepts abstracts for posters for selection by the Executive Organising Committee. Four posters were chosen for presentation in the Best of Posters Session.

Rounding out the three days of ideas and exchange of information were the final sessions, followed by the ever increasingly popular Trainees Workshop and the Joint Consumer/Study Coordinator Forum. Both of these sessions were well attended with the Trainees Workshop led by Professor Segelov and the Consumer/Study Coordinator session chaired

by Jan Mumford, Chair of the AGITG Consumer Advisory Panel.

The Closing Plenary sponsored by Roche was entitled “Implementation v Innovation – What rules in my world?” With all the changes in oncology ‘hot off the press’, how do we go from concepts to implementation? This session was presented by leaders in each field who highlighted the challenges and ‘quick wins’ in bringing advances through to the clinic.

Our ongoing gratitude goes to everyone who participates and makes this meeting a success. Special thanks go to our sponsors. The Meeting would not be possible without their support.Pictured Above Left:Ms Denise McPaul, AmgenPictured (Top L-R)1. Dr Katherine Geddes2. Dr Monica Tang, Mr Martijn Oostendorp, Dr

Desmond Yip, Ms Jenna Mitchell3. Professor John Simes4. Professor Bridget Robinson with Professor Eva

Segelov and Dr Sharon Pattison5. Dr Andrew Dean presenting at the ASM6. Amgen Exhibit at ASM

Platinum Sponsor

Gold Sponsors

Silver Sponsors

Bronze Sponsors

State of the art considerations in management of OG cancer” – involved three of our international invited speakers from the fields of medical, radiation and surgical oncology. This opening session laid the foundation for cross-discipline discussion that is a highlight of the meeting. The session covered new management options for systemic chemotherapy with Associate Professor Alcindor. New technology and methods to improve the therapeutic outcomes for patients undergoing radiotherapy for oesophageal cancer was outlined by Professor Goodman. The impact of multimodal therapy on surgical outcomes and how to strive for the best outcome for our patients was explored by Professor Reynolds.

“Responding to response – Challenging the paradigm” was a thought provoking session that considered the role of Molecular markers of prognosis and prediction presented by Professor Andrew

Barbour; and Clinical and imaging predictors of response presented by Dr Chau. Surgeon Dr Paul Cashin and radiation oncologist Professor Goodman battled it out in the debate “That complete clinical responders still require surgery for oesophageal cancer.”

A “Super MDT” session was held with Chairs, Associate Professor Nick Pavlakis (AGITG) and Professor Mark Smithers (ANZGOSA), presenting a selection of upper GI cases covering oesophago-gastric malignancy and areas of controversy. The Multi-disciplinary Team panel provided input and insights and included:

SurgeryProfessor John Reynolds, Professor David Watson, Professor Mark Smithers

Radiation OncologyProfessor Karyn Goodman, Professor Trevor Leong and Dr David Pryor

Medical OncologyAssociate Professor Thierry Alcindor, Dr Ian Chau and Dr Chris Jackson

Beginning Day Three was a Keynote Breakfast sponsored by Shire. Professor Bridgewater presented

“New data, new standards: BILCAP and New EPOC”. The New EPOC investigated whether the addition of cetuximab systemic chemotherapy in patients with resectable colorectal liver metastasis was of benefit to disease free survival. Unexpectedly, cetuximab appeared to adversely affect outcome. The mature survival data and translational analyses to date was shown. The BILCAP study investigated whether capecitabine improved overall survival compared to surveillance in patients following resection of biliary tract cancer. The outcome data was presented, including economic and quality of life analyses.

Radiation Oncologists also gathered for a breakfast session, chaired by

ANNUAL SCIENTIFIC MEETING

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Professor Chris Karapetis, AGITG Innovation Fund Award

AGITG Innovation Fund Professor Chris Karapetis from Flinders Medical Centre, Flinders University was awarded the AGITG Innovation Fund in 2017. The AGITG Innovation Fund is made possible through generous contributions from the Spencer Gibson Foundation, the His Honour Alan Bishop Fund and with donations raised through the GI Cancer Institute’s Gutsy Challenge.

Professor Karapetis received a $200,000 grant for his pilot study, titled: Prospective Study of ‘Watch and Wait’ Strategy in Patients with Rectal Cancer who have Developed a Clinical Complete Response with concurrent Chemo-radiotherapy: RENO trial (REctal cancer No Operation).

“Awarding the AGITG Innovation Fund to RENO supports a trial that has the opportunity to translate into real changes in practice for patients with rectal cancer,” commented Professor Tim Price, Chair of the AGITG and GI Cancer Institute. “RENO is a multidisciplinary study that addresses a clinical dilemma that comes up in our multi-disciplinary team meetings on a weekly basis and we are thrilled to provide funding that will hopefully determine the answers to these questions.”

According to Professor Karapetis, rectal cancer is a common malignancy and comprises a third of the cases of colorectal cancer. Currently, a combination of chemotherapy plus radiotherapy followed by surgical resection of the rectum is the standard management of locally advanced rectal cancer. Approximately 20% of patients

develop a pathological complete response to chemoradiation. In these patients, surgery may not be necessary. Professor Karapetis commented that there are retrospective studies showing the safety of a watch and wait strategy instead of surgery in patients who do not have any signs of disease after completing chemoradiation. This approach may save the patient from surgical risks and long-term morbidity.

With this study, the aim will be to assess the safety of the watch and wait approach in this population and prove the feasibility of a structured follow-up program. The study will also assess novel biomarkers, patient reported outcome measures and health economics. None of these have been studied in this population.

“It is a great honour for me to lead this study with the recognition and support that the AGITG Innovation Fund Grant provides,” said Professor Karapetis. “I anticipate that our study will guide clinical practice and I hope that findings will lead to a clinical meaningful improvement in patient outcomes. On behalf of all the investigators involved with the RENO study, I sincerely thank the AGITG and the generosity of donors to the GI Cancer Institute.”

Dr Katherine Geddes, Best New Concept Award

New Concepts SymposiumThe New Concepts Symposium, sponsored by independent biopharmaceutical company Specialised Therapeutics Australia, is a key demonstration of its commitment to cancer research and the development of new therapeutics that may change lives.

The New Concepts Symposium provides an opportunity for delegates to present embryonic new concepts for feedback and discussion with the audience, as well as comments from international guests in terms of perspective, international interest and relevance.

In 2017, the Symposium featured four high quality presentations of embryonic research concepts. This year the Award was presented to Dr Katherine Geddes for her research project, titled: The prevalence and significance of sarcopaenia in patients with operable adenocarcinoma of the stomach or gastro-oesophageal junction undergoing treatment with curative intent and the impact of altered body composition on chemotherapy delivery.

“I am very humbled to receive the Best of New Concepts Award for 2017, especially considering that the research projects presented this year were so highly commended,” said Dr Katherine Geddes. “Receiving this award from the AGITG is enormously encouraging for young female investigators and I am excited that this project, with the support received from the AGITG, might one day become a reality.”

Specialised Therapeutics Australia Chief Executive Officer Mr Carlo Montagner said he looked forward to seeing the concept evolve.

“Supporting this kind of research provides another opportunity for us to contribute to the ‘big picture’ of improving patient outcomes in the long term,” he said. “Our mission is not only to provide specialist medicines. We are committed to collaborating and contributing where appropriate, in order to make a difference.”

The AGITG thanks Specialised Therapeutics Australia for their continued support of the Best of New Concepts Symposium.

INVESTING IN RESEARCH

Merck-AGITG Clinical Research FellowshipThe inaugural Merck-AGITG Clinical Research Fellowship in Gastro-Intestinal Cancer was awarded to Dr David Lau, a clinician-scientist at the Olivia Newton-John Cancer Research Institute, Austin Hospital Melbourne. Merck provided a $150,000 grant to the AGITG to be awarded over two years to support the Fellowship. The Fellowship will provide Dr Lau an opportunity to learn from experts in GI cancer at The Royal Marsden Hospital in London in 2018.

The Managing Director of Merck Biopharma in Australia and New Zealand, Mr Drew Young, said,

“We congratulate Dr Lau on this award. Merck is very pleased to support research in GI cancer and this Fellowship provides a way to advance knowledge in this important therapy area and build links that will ultimately help to deliver better outcomes for Australian patients. We have a longstanding commitment to helping patients with colorectal

cancer as well as a significant R&D investment in a rapidly evolving pipeline of potential new cancer therapies.”

The Fellowship will contribute to efforts to develop further collaboration between the AGITG and leading research institutes in the United Kingdom.

“The overall objective of the Research Fellowship is to increase collaboration between the UK and Australia,” commented Professor Tim Price, Chair of the AGITG. “Merck’s generous support will enable Dr David Lau to not only be immersed in a UK cancer care unit but will also potentially allow for AGITG clinical trial research to be further developed in the UK. Furthermore the links that will develop by working within the UK system and Europe will also be of great value both for him and the AGITG in the future, enhancing future clinical research collaboration.”

Dr Lau’s primary focus for his research has been to discover

new molecular targets in biliary tract cancer cell lines using next generation sequencing. In addition, he has been investigating potential biomarkers for regorafenib response in the INTEGRATE trial, which formed the basis of a successful AGITG Innovation Grant in 2015 and National Health & Medical Research Council (NH&MRC) Project Grant in 2017.

“Being awarded the Merck-AGITG Clinical Research Fellowship at the Royal Marsden Hospital is an excellent opportunity to hone both my clinical and research methods amongst eminent experts in GI cancer such as Professor David Cunningham,” said Dr Lau. “On my return to Australia I would like to continue my research with newly formed international and AGITG collaborators to ultimately improve treatments and outcomes for patients with GI cancer.”

Pictured: Professor Tim price (left) Dr David Lau (centre) Mr Drew Young from Merck (right)

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Dr Melanie McCoy, Fast Forward Award

Fast Forward PresentationDr Melanie McCoy was was awarded Best Fast Forward Presentation for The Cancer Stem-Like Cell Marker SOX2 is Prognostic and May Predict Response to Chemotherapy in Colon Cancer.

Research performed at the University of Western Australia and St. John of God Subiaco Hospital has shown that new cancer cell markers may help predict which bowel cancers are most likely to return and those that will respond best to chemotherapy.

Results of this work were presented by Dr Melanie McCoy, on behalf of PhD Candidate, Tim Miller, which focussed on microscopic analysis of cancer tissues to identify a cancer cell type known as a ‘SOX2-positive stem-like cancer cell’. When tumours that contain these stem-like cancer cells are removed, it can be likened to removing a weed in the garden but leaving the root, eventually allowing the tumour to grow back from the stem-like cancer cells.

In the future, it is hoped that patients with these cells in their tumours may be able to receive targeted treatments to improve their responses to chemotherapy and their survival.

“It was a pleasure to present this work on behalf of Mr Tim Miller, who has recently submitted his PhD thesis and now plans to go on to study medicine,” said Dr McCoy. “To receive recognition from AGITG for our work is a great honour.”

Dr Rob Zielinski, Outstanding Site Award

Outstanding Site AwardRecognising their innovative Tele-trial model, the AGITG awarded the Orange Clinical Trials Centre the 2017 Outstanding Site Award.

Orange Clinical Trials Centre in Central West New South Wales is leading the way in establishing a Tele-trial pilot of a new clinical trial model that will open up the ASCOLT clinical trial to more regional and rural patients. Rural patients often experience difficulties in accessing clinical trials closer to home due to limited availability of clinical trial sites in rural and regional areas. Moreover, access to distant clinical trial sites involves long distance travel and associated expenses which pose barriers to participation of rural and regional patients in clinical trials. The tele-trial model offers an opportunity to rural and regional patients to access clinical trials. This model allows the lead clinician researcher from an established oncology clinical trial centre to consent, recruit and manage patients from rural and regional centres. The patient visits in the rural or regional centres are linked via videoconference in real time to the oncology clinical trial centre.

Upon receiving this Award, Dr Rob Zielinski, Medical Oncologist at the Orange Clinical Trials Centre, stated, “Like all cancer clinicians, the motivation for our work is providing the best care to our patients particularly enrolling them onto novel and exciting new clinical trials. Receiving this recognition as the outstanding AGITG trial site is a lovely accolade and testament to

the tireless work from our trials team, the investigators and most of all our rural patients who continue to queue up in droves for clinical trials. For too long our rural population has either missed out on clinical trials or travelled very long distances to participate. We have proven without doubt that regional NSW has a great trials team and very eager patients. More trials need to be offered to our region so we can continue to improve the cancer care for our region. The tele-trial model and the pilot will be truly ground breaking as it will be the first of its kind in Australia.”

Dr Jennifer Mooi, Best of Posters

Best of Posters The AGITG Annual Scientific Meeting accepts abstracts for posters for selection by the Organising Committee. Posters are displayed in the exhibition area and four posters are chosen for presentation in the Best of Posters Session. The winner of the 2017 Best of Posters Award, supported by Ipsen, was Dr Jennifer Mooi of the Olivia Newton-John Cancer Research Institute for her poster Exploring Consensus Molecular Subtypes (CMS) as predictors of benefit from bevacizumab in first line treatment of metastatic colorectal cancer: retrospective analysis of the MAX clinical trial.


Pictured Above Right:Viewing the Abstract Posters presented at Annual Scientific MeetingPictured (Top L-R):1. Consumer Advisory Panel with their Poster2. Professor Tim Price presenting award to Professor

Chris Karapetis3. Trainees Workshop at Annual Scientific Meeting4. Professor Tim Price presenting award to Dr Katherine

Geddes with Ms Nikoletta McLeod5. Dr Melanie McCoy, Fast Forward Award6. Dr Melanie McCoy, Dr Jennifer Mooi & Dr Margaret Lee

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Bowel cancer, the second most common cancer affecting people in Australia, is a disease with diverse outcomes and which responds in varying ways to treatment. Bevacizumab is a drug commonly used to treat bowel cancer which works by slowing the growth of new blood vessels needed by tumours to grow. The AGITG has previously sponsored the MAX clinical trial, which showed the benefit of bevacizumab when added to standard chemotherapy treatment. However, not all patients with bowel cancer respond to this treatment, and currently no test exists to predict which patients will or will not respond to bevacizumab. Using tumour samples collected from patients treated on the MAX clinical trial, we were able to analyse and classify these tumours into four “molecular subgroups” according to patterns of genes expressed in the tumour. By classifying patients’ tumours in this way, we found that two out of the four molecular subgroups of bowel cancer

respond better to bevacizumab. This classification test is not yet widely available in clinic, and more testing is required to confirm these results, but nevertheless these are exciting and positive findings that could potentially change the way we select treatment for bowel cancer patients in the near future.

“It’s an honour to receive an award like this from your peers in recognition of the work you’ve done,” said Dr Jennifer Mooi. “It gives me encouragement to keep going and know I am on the right track! Thank you to Ipsen for supporting these awards.”

“At Ipsen, our commitment is to enhance patient care,” said Peter Koetsier, General Manager Australia and New Zealand, Ipsen. “We are proud that this contribution for Best of Posters is able to help recognise excellent research and positive outcomes for patients”. The AGITG is grateful for sponsorship from Ipsen for the Best of Posters.

Attendees at the Preceptorship

Preceptorship in Upper GI CancerThe 2017 AGITG Preceptorship in Upper GI Cancer was held in May in Surfers Paradise, Queensland.

This two-day intensive learning course is based on a complete review of literature to understand the evolution of treatment for Upper GI Cancer in the context of current treatment paradigms. The Harvard Short Course model is used, with learning in small-group interactive sessions. Aimed at advanced trainees and junior consultants in Medical, Radiation and Surgical Oncology, the format was that of a short course (retreat) with learning in small groups and active participation from attendees with


regard to reviewing papers and presenting cases.

Topics that were covered included basic biology and translational science of Upper GI Cancer and current therapies, seminal papers in adjuvant therapy of Upper GI Cancer, seminal papers in therapy of metastatic Upper GI Cancer, treatment paradigms for metastatic Upper GI Cancer and treatment pathways to achieve cure.

The Preceptorship was convened by Professor Eva Segelov and Preceptors included Professor Eva Segelov, Dr Lorraine Chantrill, Professor Chris Karapetis, and Associate Professor Jeremy Shapiro.

Participants at CommNETs

CommNETs Research Collaboration The third meeting of the Commonwealth Neuroendocrine Tumour Collaboration (CommNETs) was held in December to continue to review gaps in NET research.

The two-day meeting included participation of members from Australia, Canada and New Zealand engaging in active collaboration, moving current projects forward and developing new working groups.

The meeting opened with a summary of the achievements of 2017, including:

• The formal MOU between AGITG and CCTG

• The generation of an Executive Committee and Project Oversight Committee

• Presentations of posters at ENETS and ESMO

• Oral presentations at ASCO GI and ESMO

• The NET preceptorship held in Singapore in November with attendees from eight countries.

The first day was spent updating and working on current projects. The amount of work that has been achieved over a year was encouraging to see. The group confirmed the intention that all members should be actively involved in at least one project, and that attendance at future CommNETs meetings be reliant on project involvement. The theme of collaboration continued into the evening with the quiz led by Quiz Master Eva Segelov, which was won by team “Kwozzies”.

Day two of the meeting began with a walk up Lē’ahi (Diamond Head) for a select hardy group followed by a new concept session. Here the CABERNET clinical trial (Principal Investigator: Professor David Ransom) and NET SANGUIS trial (Principal Investigator: Professor Michael Michael) were introduced, and a Nutrition in NETs working group proposed (Principal Investigator: Erin Kennedy). The main project for day two was an adapted Delphi process as the starting point for developing indicators for NETs, and the generation of a new working group to support this project (Principal Investigator: Dr Ben Lawrence).

It was decided that the main projects that CommNETs would focus on in 2018 is the development of clinical trials, with the CommNETs 2018 meeting likely to be a focused meeting to generate two clinical trial protocols. Further information and expressions of interest will be forthcoming. A fourth CommNETs ASM has been proposed for early 2019.

Dr Monica Tang, AGITG Fellow

AGITG Fellowship Program In 2017, Dr Monica Tang and Dr Namrata Nayar were offered Research Fellowships with the AGITG. Research Fellows provide academic and clinical expertise for particular areas of research or specific projects.

Dr Nayar said that the research fellowship provided her with a platform to enhance her understanding of design and conduct of clinical trials and learn skills to develop and transform a concept into a mature trial. She was also able to deepen her understanding of the operational aspects of large collaborative trial groups. During her oncology training years she developed a special interest in GI cancer. She found GI cancer a challenge as there are still gaps in evidence and unmet needs in some tumour subtypes which she hopes can be addressed through clinical trials.

Dr Monica Tang has found GI cancers of great interest as they encompass a range of malignancies, with different biologies and treatments. Dr Tang found the Research Fellowship provided her with a way to learn more about how clinical trials are developed and coordinated. She is developing skills in designing and implementing trials to improve outcomes for patients.

Pictured Above Left: Participants at CommNETs Research Collaboration

46 47

In 2015, the Ronald Geoffrey Arnott Foundation, The Jessica & Wallace Hore Foundation, Perpetual Foundation – Elaine Haworth Charitable Endowment and Perpetual Foundation – The Merrett Endowment generously supported two AGITG translational research projects in colorectal cancer.

Project TitleDo low frequency somatic RAS mutations confer resistance to EGFR monoclonal antibody therapy in patients with metastatic colorectal cancer?

This funding enabled Professor Paul Waring and the team at the Centre for Translational Pathology at the University of Melbourne to determine whether patients with metastatic colorectal cancer whose tumours possess low frequency RAS gene mutations survive longer or not following treatment with the epidermal growth factor receptor monoclonal antibody, cetuximab. The CO.17 clinical trial, conducted by the AGITG in collaboration with the National Cancer Institute of Canada (NCIC), changed clinical practice worldwide by showing that patients with tumours harbouring high frequency (>20%) KRAS mutations do not have a survival benefit following cetuximab. However, subsequent smaller inconclusive studies, using more sensitive assays, suggested that patients with low (5-20%) and perhaps ultra-low (0.01-5%) frequency RAS mutations may also not benefit. Using samples from the AGITG-NCIC CO.17 and CO.20 trials the project retrospectively screened tumour samples, using an ultra-sensitive assay, from 1105 trial participants with KRAS wild type (WT) tumours to determine whether or

not subjects with low and ultra-low frequency RAS mutations survive longer following cetuximab.

Research OutcomesThe first objective was to determine the prevalence of de novo low frequency RAS mutations in the WT populations. To eliminate the possibility of any residual false positive low frequency mutations due to sample cross-contamination, DNA polymerase errors and formalin-induced DNA modifications, only low frequency mutation as seen in three independent replicates (or both duplicates if one failed) were accepted as genuine (true positive) low frequency RAS mutations.

The second objective was to demonstrate that the assessable CO.20 and CO.17 subgroups were representative of the entire clinical trial cohorts in terms of demographics and clinical outcomes. For CO.20, the overall response rate (ORR) was 9.5% and there was a significant difference in progression-free survival (PFS) (HR 0.56, 95% CI: 0.378-0.82, p=0.0034) and overall survival (OS) (HR 0.62, 95% CI 0.42-0.90, p=0.013) between the RAS high frequency mutant (HFMT) and wild type (WT) groups. Notably, the ORR in the HFMT group was only 5.8%. For CO.17, the overall response rate (ORR) was 4.95% and there was a significant difference in progression-free survival (PFS) (3.0 vs 1.8 months HR 0.58, 95% CI: 0.43 – 0.77, p=0.0006) and overall survival (OS) (6.5 vs 5.0 months, HR 0.65, 95% CI 0.47 – 0.90, p=0.009) between the wild type (WT) and RAS high frequency mutant (HFMT) groups. Notably, the ORR in the HFMT group was 0%. These are as expected, indicating that the subgroups are indeed representative of the entire cohort.

The third objective was to determine the prevalence of true positive low frequency RAS mutations (LFMT).

There were 5 subjects with LFMT in CO.20 (2.6%) and 2 in CO.17 (1%). Notably, there were no polyclonal LFMT and 6 of 7 LFMT were in KRAS exon2 or 3 with one NRAS exon 3 mutation, indicating no obvious enrichment of polyclonal or non - KRAS exon 2 mutations as seen in the acquired drug resistant mutations.

The fourth objective was to determine the clinical significance of LFMT. There was no difference in both CO.20 and C0.17 with ORR, PFS or OS comparing the LFMT group with the WT or HFMT groups, although the number of subjects with LFMT in all three triplicates is too low (n=7) to draw meaningful conclusions.

Further analysis will include (a) concordance with the Beaming method, (b) an examination of the prevalence and clinical significance of LFMT seen in one and two replicates only and (c) to determine by the minimum p method the optimal cut off between low and high frequency RAS mutations by mutant allele frequencies using CO.20 as a training set and CO.17 as an independent test set.

The conclusion that low frequency RAS mutations present at >0.1% are rare (2%) in untreated primary and metastatic colorectal cancers and when present are, unlike high frequency mutations (>5%), of no clinical significance. They also show no enrichment of NRAS or polyclonal mutations commonly seen in acquired RAS mutations following treatment with EGFR monoclonal therapy. The practical significance of our findings is that in the vast majority of cases the results of RAS mutations testing should give unequivocal results regardless of the assay cut point used and that diagnostic pathology laboratories need not be too concerned about missing an occasional low frequency RAS mutation.

PERPETUAL GRANTS ACQUITTED IN ��

Project Title Who benefits from aspirin? A translational study of samples collected on the international ASCOLT adjuvant colorectal cancer aspirin trial.

This funding assisted AGITG ASCOLT study Investigator Professor Eva Segelov in collaboration with Dr Oliver Sieber and the team at the Walter and Eliza Hall Institute of Medical Research to analyse genetic changes in colorectal cancers that predict behaviour of the cancer and whether it will recur. This analysis was based on tissue and blood samples from patients enrolled in the international Phase III ASCOLT study being conducted by the AGITG and international partners. The

effect of aspirin on cancer recurrence and its mechanism of action was studied in patients who have received either aspirin or placebo in a blinded design. It was anticipated that, on the basis of finding genetic markers, a profile to identify the patient subgroup that benefit from aspirin will be identified. This translational research is unique as the biospecimens have been obtained with consent on the only prospective adjuvant aspirin trial being conducted worldwide.

Research OutcomesThis study has resulted in a detailed survey of tumour molecular aberrations for 150 Australian patients with colorectal cancer participating in the ASCOLT clinical

trial. This data constitutes the foundation of detailed biomarker discovery and validation studies for the entire trail cohort for which additional funding has now been secured. Final data analysis and publication will occur upon completion of the trial.

Due to the generosity of these donors, these projects have supported better health outcomes for people with GI cancers in Australia and internationally and have addressed key unanswered questions.

Pictured: Professor Paul Waring recipient of this grant for metastatic colorectal cancer research.

48 49

Operations Executive

Committee

BOARD OF DIRECTORS

Consumer Advisory Panel

Scientific Meeting

Committtee

Scientific Advisory

Committee

Independent Data Monitoring

Committee

Finance & Risk Management

Commitee

Chief Executive

Officer

International Development

Committee

Corporate Governance Committee

AGITG & GI CANCER INSTITUTE ORGANISATIONAL STRUCTURE

FinanceMarketing,

Fundraising & Communications

Administration

Trial Management Committees

Lower GI Working Party

Upper GI Working Party

Infrastructure GrantsFunds provided by Cancer Australia to support AGITG infrastructure are managed by the University of Sydney NHMRC Clinical Trials Centre. These funds are not reported in the financial accounts of the AGITG, unless transferred to support of specific AGITG expenses.

Funding• Cancer Australia infrastructure

grants: During the 2017 year a further extension was granted to 30 June 2018. From these grant extensions the AGITG received $230,800 to support infrastructure costs for the financial year.

Research GrantsFunds provided by Cancer Australia, Cancer Council and the National Health and Medical Research Council in support of trial coordination are also managed by the University of Sydney NHMRC Clinical Trials Centre. Funds to support site payments and insurance costs relating to these studies are transferred to the AGITG and are reflected in these financial accounts.

Community GrantsSupport for expenditure on Community activities during the 2017 year came from the Newman’s Own Foundation for $19,935 which was received in 2015.

Grants contributing to AGITG trials conducted during the 2017 financial year are outlined below. Grant income and expenditure during the 2017 year for these trials are included in the 2017 Income Statement.

ALaCaRT: A phase III prospective randomised trial comparing laparoscopic assisted resection versus open resection for rectal cancer.

Funding• NHMRC Grant: $932,586 (2011)• NHMRC Grant: $573,259 (2015)

ASCOLT: An international randomised, double blind, placebo controlled phase III multi-centre trial, investigating the effect of aspirin on disease-free and overall survival as adjuvant treatment in patients with resected stage II and III colorectal cancer.

Funding• Cancer Australia and Bowel Cancer

Australia Grant: $328,000 (2014)

ASCOLT Translational Study: A translational study of samples collected on the international ASCOLT adjuvant colorectal cancer aspirin trial.

FundingPerpetual Trustee Company Limited (2015)

• The Jessica & Wallace Hore Foundation: $25,000

• Elaine Haworth Charitable Endowment: $41,522

• The Merrett Endowment: $35,922

CO.20 and CO.17 Translational Research: Low-Frequency KRAS Mutations as a Predictive Biomarker for Cetuximab Resistance (the “KRAS Project”).

FundingPerpetual Trustee Company Limited (2015)

• Ronald Geoffrey Arnott Foundation: $108,000

DOCTOR: A randomised phase II trial of pre-operative cisplatin, 5-fluorouracil and docetaxel or cisplatin, 5-fluorouracil, docetaxel plus radiotherapy based on poor early response to standard chemotherapy for resectable adenocarcinoma of the oesophagus and/or oesophageal junction.

Funding• NHMRC Grant: $387,000 (2011)

TOPGEAR NHMRC: A randomised phase II/III trial of pre-operative chemoradiotherapy versus pre-operative chemotherapy for resectable gastric cancer.

Funding • NHMRC Grant: $756,136 (2013)

CONTROL NETS: Capecitabine ON Temozolomide Radionuclide therapy Octreotate Lutetium-177 NeuroEndocrine Tumours Study.

Funding• Unicorn Foundation: $200,000

(2015), and $105,000 (2017)• University of Sydney Bridging

Grant: $30,000 (2015)

NABNEC: A Randomised Phase II Study of NAB-Paclitaxel In Combination With Carboplatin As First Line Treatment of Gastrointestinal Neuroendocrine Carcinomas.

Funding• NHMRC project grant: $360,750

(2016)

ACTICCA: A multi-centre, prospective, randomised, controlled phase III trial designed to assess the clinical performance of gemcitabine with cisplatin and observation vs. observation alone in patients after curative intent resection of Biliary Tract Cancer (BTC).

Funding• Cancer Australia Grant: $140,000

(2016)

SCOT: Short Course Oncology Therapy - A study of adjuvant chemotherapy in colorectal cancer.

Funding• NHMRC Grant: $399,700 (2009)

SPAR: Simvastatin with chemotherapy and radiation in preoperative treatment for rectal cancer: a randomized, placebo-controlled phase 2 trial.

Funding• CSNZ Grant: $149,000 (2015)• CCNSW Grant: $450,000 (2016)• CA Grant: $147,000 (2017)

GRANTS

Public Affairs, Marketing & Fundraising Committee

50 51

BOARD OF DIRECTORS

Professor Tim Price Chair MBBS DHthSc (Med) FRACPTim is Senior Consultant Medical Oncologist and Director of Medical Oncology and Clinical Cancer Research at The Queen Elizabeth Hospital in Adelaide. His major clinical interest is in treatment of patients with gastro-intestinal cancer and he is currently involved in an extensive gastro-intestinal clinical trial program. He is Professor at the University of Adelaide and Colorectal Cancer Stream leader for the South Australian Health and Medical Research Institute, and leads the gastro-intestinal translational and laboratory research laboratory at the Basil Hetzel Institute. He chairs the current national NHMRC Cancer Council Colorectal Guidelines committee which led to the recently published update. He is also a visiting/honorary Professor at University of Sydney and University of Antwerp.AGITG Committee Positions:Chair, Scientific Advisory CommitteeMember, Corporate Governance CommitteeMember, Upper GI Working PartyMember, Operations Executive Committee

Associate Professor Niall TebbuttDeputy Chair & TreasurerPhD MRCP FRACPNiall trained at Oxford University in the UK and has extensive experience in the management of patients with gastro-intestinal cancer. He has a strong involvement in clinical research and has initiated several investigator-led clinical trials and AGITG led clinical trials. He is Director of Medical Oncology at the Olivia Newton-John Cancer Research and Wellness Centre and has published over 140 manuscripts. He has also led fundraising climbs up two peaks – Kilimanjaro and Aconcagua, collectively raising over $280,000 for gastro-intestinal cancer research.AGITG Committee Positions:Chair, Finance & Risk Management Committee Chair, Lower GI Working Party Member, Scientific Advisory Committee

Professor John SimesGroup CoordinatorBSc MBBS SM FRACP MDJohn is an NHMRC Senior Principal Research Fellow and Director, NHMRC Clinical Trials Centre, University of Sydney and the AGITG Coordinating Centre at the NHMRC Clinical Trials Centre. He is Professor of Clinical Epidemiology, Sydney Medical School, University of Sydney and a Medical Oncologist, Royal Prince Alfred Hospital, and Chris O’Brien Lifehouse, Sydney. He is also Director of the Sydney Catalyst Translational Cancer Research Centre and a Co-Founding Director of the Australian Clinical Trials Alliance. John has a long-standing interest in major clinical trials research aimed to improve practice and health outcomes including in gastro-intestinal cancer. John has been a founding member of AGITG since 1991 and a member of the AGITG Board since its incorporation in 2000.AGITG Committee Positions:Member, Scientific Advisory CommitteeMember, Upper GI Working PartyMember, Lower GI Working PartyChair, Operations Executive Committee

Pictured (L-R) Board of Directors: Mr Michael Gordon, Ms Christine Liddy AO, Professor John Simes, Professor Bridget Robinson, Dr Lorraine Chantrill, Professor Tim Price (Chair), Professor Trevor Leong, Professor Eva Segelov, Mr Dan Kent, Professor David Watson, Associate Professor Niall Tebbutt (Deputy Chair)

I am proud to chair a Board of Directors with such a high level of expertise and passion. Having the opportunity to work with a group of such qualified professionals who are highly committed to GI cancer research is a privilege.

Professor Tim Price

Board ofDirectors

52 53

Mr Dan KentGrad.Dip.Mgmt

Dan retired as Chair of the AGITG/GI Cancer Institute Consumer Advisory Panel (CAP) in May 2017 – a role he had undertaken for six years after joining the CAP as a founding member in 2008. In 2015 Dan was presented with the Inaugural AGITG ‘John Zalcberg OAM Award for Excellence in AGITG Research’ in recognition of his significant and outstanding leadership contribution to AGITG research over a sustained period. Dan brings a wealth of experience through his active involvement in the AGITG/GI Cancer Institute in a leadership capacity, his involvement in other external groups, his managerial experiences as Director of Bundaberg Distilling and Bundaberg Rum companies 1988-2000 and holding Fellow memberships of the Certified Practising Accountants and the Australian Institute of Management, as well as lived experience as a rectal cancer survivor.AGITG Committee Positions:Chair, Consumer Advisory Panel – until May 2017Member, Finance & Risk Management CommitteeMember, Public Affairs, Marketing & Fundraising CommitteeMember, Corporate Governance Committee

Dr Lorraine ChantrillB.Sc.(Hons) MBBS(Hons) FRACP PhD

Lorraine is Senior Staff Specialist Medical Oncologist at St Vincent’s Hospital is actively the Clinical Director of Medical Oncology Clinical Trials at St Vincent’s Hospital. She has served on the AGITG Upper GI Working Party since inception in 2011 and has chaired the Working Party since August 2014. She was appointed to the Board of Directors of AGITG in August 2016. Lorraine is co-chair of the AGITG/Australasian Pancreatic Club Pancreas Cancer Research Workshop (since 2013) and an executive member of the Australasian Pancreatic Genome Initiative and the Australasian Pancreatic Club. She has recently been appointed to the Data Safety Monitoring Board of the Australasian Leukaemia and Lymphoma Group. She completed a PhD by research in the Pancreas Cancer Group at The Kinghorn Cancer Centre and has a special interest in the molecular biology of pancreas cancer.AGITG Committee Positions:Chair, Upper GI Working PartyMember, Scientific Advisory CommitteeCo-Chair, AGITG-APC Pancreas Cancer Research WorkshopMember, Public Affairs, Marketing & Fundraising Committee

Professor David WatsonMBBS FRACS MD

David is Professor of Surgery in the College of Medicine and Public Health at Flinders University and an Oesophago-gastric Surgeon at Flinders Medical Centre. His research interests include clinical and biological aspects of benign and malignant oesophageal disease, including molecular biology of Barrett’s oesophagus and oesophageal carcinoma. David is a Past President of the Australia and New Zealand Gastric and Oesophageal Surgery Association.AGITG Committee Positions:Member, Corporate Governance CommitteeMember, Scientific Advisory Committee

Professor Bridget Robinson BMedSc MD (Otago) FRACP

Bridget graduated in Medicine from the University of Otago, then undertook postgraduate training and MD research at the Royal Marsden Hospital and Institute for Cancer Research in London, before returning to a position as Medical Oncologist at Christchurch Hospital. Since 1998 she held a joint appointment at the University of Otago and the CDHB, and in 2010 was appointed to the Mackenzie Chair in Cancer Medicine. She initiated and directs the Cancer Society Tissue Bank to support research, and is clinical director of the Mackenzie Cancer Research Group. Her research interests include colorectal cancer, tumour stroma, and effects of obesity, coagulation in cancer, familial cancer, and translational research, as well as clinical trials in cancer patients. Her clinical practice includes breast and colorectal cancers, neuroendocrine tumours, sarcoma’s including GIST. She chairs the Canterbury Comprehensive Cancer Centre.AGITG Committee Positions:Member, Lower GI Working Party

Ms Christine McNamee Liddy AOFAICD BA UNSW

Christine is a former Board Member and Past President of the Royal Flying Doctor Service (RFDS) of Australia and former National Vice President of the RFDS. She is also a member of the Board of The University of NSW Foundation and Member of the Advisory Board, Faculty Arts & Social Sciences, UNSW and the Dame Pattie Menzies Foundation. She is a Fellow and Council Member of St John’s College within the University of Sydney and a Council Member of the Friends of the Sydney International Piano Competition, an Advisory Board Member of the Mosman Art Gallery, and former member of the Digitization Committee of the State Library of NSW and the RFDS Capital Campaign Committee. Christine is also a former Board Member Frontline Defence Services Australian Army and Air Force and former Secretary of the Art Gallery Society of NSW (AGNSW). Currently, she is Managing Partner Australian Plantscapes and former Managing Partner of All Purpose Indoor Plant Hire.AGITG Committee Positions:Chair, Public Affairs, Marketing & Fundraising CommitteeChair, Corporate Governance CommitteeMember, Finance & Risk Management CommitteeMember, Scientific Advisory Committee

Mr Michael GordonBBus

Michael is an independent company director serving on the boards and investment committees of companies in the financial services industry both here in Australia and internationally. He is a Director of Blue Sky Alternative Investments Limited where he also chairs the Nominations and Remuneration Committee and is a member of the Audit Committee. Michael is a Director of Total Risk Management Pty Limited, a subsidiary of Russell Investments which is trustee of the Russell Investments SuperSolution Master Trust and he also chairs the Investment Committee. Michael chairs the FWD Group Investment Committee in Asia and also sits on both the Investment Advisory Committee of Altius Investment Management in Sydney as well as the Investment Committee for a large family office. He has had a distinguished career as a leading investment professional with Perpetual, BNP Paribas, Fidelity International and Schroders.AGITG Committee Positions:Member, Finance & Risk Management CommitteeMember, Public Affairs, Marketing & Fundraising Committee – until May 2017

BOARD OF DIRECTORS

Professor Trevor LeongCompany SecretaryMBBS, MD, FRANZCRTrevor is Director of Radiation Oncology at Peter MacCallum Cancer Centre. He is an academic radiation oncologist, is actively involved with clinical research programs and has been a principal investigator in numerous phase I/II/III studies relating to gastro-intestinal malignancies. He has been involved with AGITG activities for over 10 years as a trial investigator, member of the Scientific Advisory Committee, and Board member.AGITG Committee Positions:Member, Corporate Governance CommitteeMember, Upper GI Working PartyMember, Scientific Advisory Committee

Professor Eva SegelovMBBS (Hons1) FRACP PhD

Eva is a Medical Oncologist and is Director of Oncology at Monash University and Monash Health, Melbourne, Victoria, previously Senior Medical Oncologist at St Vincent’s Hospital, St Vincent’s Private Hospital and St Vincent’s Clinic and Associate Professor of Medicine, University of New South Wales. She has an interest in academic clinical trials in gastro-intestinal and breast cancer and has been a member of the AGITG since 2003. She has clinical trials expertise, links with national and international trials groups, and extensive experience with adult medical education.AGITG Committee Positions:Chair, Annual Scientific Meeting Organising CommitteeChair, Education CommitteeMember, Scientific Advisory CommitteeMember, Lower GI Working PartyCo-Chair, Commonwealth Neuroendocrine Tumour Collaboration (CommNETs)

54 55

Scientific Advisory CommitteeThe Scientific Advisory Committee (SAC) is the focal point for widespread discussion of research ideas. Its members, who are drawn from the AGITG and the NHMRC Clinical Trials Centre (CTC), are experts in the fields of medical oncology, surgery, radiation oncology, biological research, quality of life research, statistics, study coordination and consumers.

The SAC’s key role is to determine the research priorities of the AGITG. The committee’s open dialogue leads to the development of a common language, interaction and commitment to trials by a broad range of medical specialists, allied health professionals and consumers.

SAC meetings foster a spirit of collaboration and cohesion between a diverse group of people who share a common goal: to improve patient care through GI cancer clinical trials.

Upper GI and Lower GI Working PartiesThe AGITG’s Upper GI and Lower GI Working Parties represent the disciplines of medical oncology, surgery, radiation oncology, statistics, translational science and study coordination. The Upper GI Working Party focuses on cancers of the oesophagus, gallbladder, pancreas, stomach and liver, while the Lower GI Working Party looks at cancer of the bowel, rectum and anus.

The working parties meet bi-monthly to:• Identify gaps in research activities;• Develop and/or facilitate new

clinical research concepts;• Review the scientific merit of

research proposals;• Explore funding and feasibility

opportunities in liaison with the Operations Executive Committee;

• Nominate Principal Investigators;• Nominate Trial Management

Committee members.

SCIENTIFIC ADVISORY COMMITTEE & WORKING PARTIES

Scientific Advisory CommitteeProfessor Tim Price Chair, Medical OncologistProfessor Steve Ackland Medical OncologistProfessor Andrew Barbour SurgeonDr Lorraine Chantrill Medical Oncologist Professor Stephen Clarke Medical OncologistProfessor Michael Findlay Medical OncologistProfessor Val Gebski StatisticianConjoint Professor David Goldstein Medical OncologistMr Peter Hewett SurgeonProfessor David Joseph Radiation OncologistMr Dan Kent AGITG Board Professor Trevor Leong Radiation OncologistMs Christine Liddy AO AGITG BoardMrs Jan Mumford Chair, Consumer Advisory Panel Professor Bridget RobinsonMedical Oncologist Professor Eva Segelov Medical OncologistDr Jennifer Shannon Medical OncologistProfessor John Simes Medical OncologistDr Katrin Sjoquist Medical OncologistMs Anne Smith Clinical Research ManagerClinical Professor Nigel Spry Radiation OncologistDr Andrew Stevenson SurgeonAssociate Professor Niall Tebbutt Medical OncologistProfessor David Watson SurgeonDr Sonia Yip Oncology Translational ResearcherProfessor John ZalcbergMedical OncologistProfessor Nik Zeps Biological Scientist

Upper GI Working Party Dr Lorraine Chantrill Chair, Medical OncologistProfessor Andrew Barbour Deputy Chair, SurgeonProfessor Alexander BoussioutasGastroenterologistMs Katie Benton DieticianDr Yu Jo ChuaMedical OncologistProfessor Jonathan Fawcett SurgeonProfessor Michael Findlay Medical OncologistProfessor Val Gebski StatisticianDr Koroush Haghighi SurgeonProfessor Trevor Leong Radiation OncologistAssociate Professor Lara Lipton Medical OncologistMrs Jan MumfordChair, Consumer Advisory PanelAssociate Professor Nick Pavlakis Medical OncologistProfessor Tim Price Medical OncologistDr Amy Shorthouse Radiation OncologistProfessor John Simes Medical OncologistDr Katrin Sjoquist Medical OncologistMs Belinda Steer DieticianClinical Professor Nigel Spry Radiation OncologistDr Sonia Yip Oncology Translational Researcher

Lower GI Working Party Associate Professor Niall Tebbutt Chair, Medical OncologistProfessor Chris Karapetis Deputy Chair, Medical OncologistDr Matthew Burge Medical OncologistDr Jayesh Desai Medical OncologistMr Alexander Heriot SurgeonMr Peter Hewett SurgeonProfessor David Joseph Radiation OncologyDr Ben Markman Medical OncologistDr Paul McMurrick SurgeonMr Robin Mitchell Deputy Chair, Consumer Advisory PanelDr Sam Ngan Radiation OncologyProfessor Bridget Robinson Medical OncologistProfessor Eva Segelov Medical OncologistAssociate Professor Jeremy ShapiroMedical OncologistProfessor John Simes Medical OncologistDr Katrin Sjoquist Medical OncologistDr Sonia Yip Oncology Translational ResearcherProfessor Nik Zeps Biological Scientist

Pictured: Professor Stephen Ackland at the Annual Scientific Meeting

56 57

For the AGITG, 2017 has been successful in the face of several challenges. Such success is measured by the pursuit of scientific research to improve the treatment of gastro-intestinal cancers, aligned with the sound financial management of the Company. This has been achieved through the increased role which Senior Management have embraced and driven in managing the scientific research for the benefit of the global community.

The 2017 financial year has resulted in a deficit result from Operations of $102,709. However, the Reserves have increased by $914,027 and the net assets have grown from $5,936,084 in 2016 to $6,731,312 in 2017. The assets are managed to fund current and future research projects, to develop the marketing and fundraising program and to operate the business of the company in an effective and sustainable manner.

This growth in net assets has been achieved in an increasingly competitive environment where opportunities for government and non-government grants and support are reducing. Strategies that have been adopted to meet this challenge include a strengthened commercial view of opportunities, expanding revenue streams, reviewing the nature and risk profile of investable funds, and exploring opportunities with the Medical Research Future Fund.

The funding from Cancer Australia and the NHMRC to support the conduct of scientific trials and the infrastructure costs associated with these trials, has been important to provide core funding to the AGITG.

This support recognises the crucial need to support the infrastructure to operate and manage scientific trials in addition to the funding required to conduct the trials themselves.

Our strategy includes a view to our future. Improving our brand recognition in both the public and professional sectors, furthering the donor support and effective use of that support through our Reserves strategy will have ongoing benefits to the activities of the AGITG. During the year, our fundraising program was reviewed in conjunction with industry consultants. I am pleased to report that our approach has been sound and is consistent with industry standards. Changes have been implemented to further develop specific areas of our fundraising program, which we anticipate, will further improve our community engagement and our financial opportunities.

AGITG continues to provide funding for the Innovation Fund and to support pilot studies, unfunded trials and to initiate trial development. Other initiatives that AGITG supports and funds, include the Annual Scientific Meeting, CommNETs, and the Preceptorship programs, providing opportunities to support various sectors of the scientific community. These activities also enable the work of the AGITG to be promoted, the outcomes from the research to be communicated and the talent from within the network of the company to engage with the scientific and the general community.

Contributions from government, industry, institutions, investments, donors and members provides the resource framework and the scope from which the company is able to pursue its objectives and central purpose. We appreciate and respect their support to date and in the future.

I am grateful for the dedicated and professional support from the members of the Finance and Risk Management Committee, our CEO, and the support team within the AGITG and external accountants Walker Wayland Pty Ltd. Their ongoing engagement to improve what and how we operate allows the Board to focus on our core objectives with confidence and sound guidance on our financial position.

Associate Professor Niall Tebbutt PhD MRCP FRACP Deputy Chair & Treasurer

TREASURER’S REPORT

I wanted the Aconcagua Gutsy Challenge to be a genuine challenge. We knew at the beginning that the stats are that about one in four people who tackle it make the summit. We all knew we were doing something that was difficult but we wanted to raise funds to support the one in ten people who will be diagnosed with GI cancer in Australia this year.

Associate Professor Niall Tebbutt

58 59

STATEMENT OF PROFIT OR LOSS AND OTHER COMPREHENSIVE INCOME FOR THE YEAR ENDED 31 DECEMBER 2017

2017 2016

$ $

Revenue 5,389,955 4,457,817

Other income 1,638,850 1,382,835

Administration/Infrastructure expense (410,757) (448,629)

Depreciation and amortisation expense (64,101) (9,590)

Trial and Site Costs (5,259,554) (3,691,570)

Scientific Events (923,165) (790,392)

Marketing/Fund Raising costs (473,937) (445,334)

(Deficit) / Surplus before income tax (102,709) (455,137)

Income tax expense - -

(Deficit) / Surplus for the year (102,709) (455,137)

(Deficit) / Surplus for the year (102,709) (455,137)

Other comprehensive income after income tax

Other comprehensive income for the year, net of tax - -

Total comprehensive income for the year (102,709) (455,137)

Total comprehensive income attributable to members of the entity (102,709) (455,137)

These Financial pages are an extract from the audited accounts for the financial year ended 31 December 2017.

STATEMENT OF FINANCIAL POSITION AS AT 31 DECEMBER 2017

2017 2016

$ $

Assets

CURRENT ASSETS

Cash and cash equivalents 3,924,432 5,146,370

Financial Assets 8,291,418 7,785,863

Trade and other receivables 1,231,774 678,404

Other assets 96,293 74,379

TOTAL CURRENT ASSETS 13,543,917 13,685,016

NON-CURRENT ASSETS

Property, plant and equipment - -

Intangible assets 71,210 64,521

TOTAL NON-CURRENT ASSETS 71,210 64,521

TOTAL ASSETS 13,615,127 13,749,537

Liabilities

CURRENT LIABILITIES

Trade and other payables 1,141,393 404,712

Other short term liabilities 2,451,668 5,383,671

TOTAL CURRENT LIABILITIES 3,593,061 5,788,383

NON-CURRENT LIABILITIES

Long-term provisions 64,309 56,812

Other long term liabilities 3,226,446 1,969,258

TOTAL NON-CURRENT LIABILITIES 3,290,755 2,026,070

TOTAL LIABILITIES 6,883,816 7,814,453

NET ASSETS 6,731,311 5,935,084

EQUITY

Reserves 3,471,181 2,557,154

Retained Earnings 3,260,130 3,377,930

TOTAL EQUITY 6,731,311 5,935,084

CONTINGENT LIABILITY - -

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YOUR SUPPORT MAKES THE DIFFERENCE

Thanks to the support from our committed and passionate supporters, we continue to develop breakthroughs and improvements in medical practice for people with GI Cancer. Community support is critical to providing the answers to the many unanswered questions, one day ultimately making GI cancer a disease of the past. There have been a number of ways our supporters have made a difference to the lives of people diagnosed with GI cancer, their families and future generations.

DonationsThrough our regular appeals, donations have been received which enable us to conduct our clinical trials that lead to better health outcomes for patients. All donations, no matter what size, have contributed to trials initiated this past year. We also have continued to receive and grow the number of regular giving supporters – which provides us with the financial stability that allows us to plan for the future.

To make an online donation please visit www.gicancer.org.au/donate

The Gutsy ChallengeThis year we have had over 70 people participate in one of our fun Gutsy Challenge activities. This has

included participation in our 100 Runs initiative, taking on a sugar-free challenge, our Larapinta Gutsy Challenge and Aconcagua Gutsy Challenge, and participation in the Dom Colagiuri Cup - a five-a-side football competition. These have been undertaken by individuals and groups of friends or colleagues who wanted to ‘Get Gutsy for GI Cancer Research’. To learn more see www.gicancer.org.au/gutsy

BequestsWe were privileged to receive bequests from two generous supporters during the year. Through leaving a gift in their Will, these supporters have left a legacy for future generations. There are many reasons why people choose to

leave a bequest – most often it is a very personal decision. No matter whether the donation is large or small, bequests enable cutting edge research into new treatments for patients diagnosed with GI Cancer beyond our lifetime.

To learn more see www.gicancer.org.au/yourwill or for a confidential conversation please call Nicky on 1300 666 769.

Honouring a Loved OneWe are very grateful for those family members who have lost someone during the year and chosen to honour their loved one through In Memory donations, often collected during the funeral in lieu of flowers. These donations create something positive by supporting innovative research for improved outcomes for future generations.

To arrange for personalised In Memory donation cards or for more information please contact Alaine on 1300 666 769.

Living Room Community EventsIn 2017 we held our annual Living Room Event at the Chris O’Brien Lifehouse in Sydney to coincide with Pancreatic Cancer Awareness Month. Our Sydney supporters interested in Pancreatic Cancer were invited to hear from leading researchers and medical oncologists – Professor David Goldstein and Dr Lorraine Chantrill. Both speakers presented on the progress being made in developing improved treatments for pancreatic cancer patients and provided an update on results from one of our recent pancreatic cancer research trials.

For more please view the event video via www.gicancer.org.au/livingroom

VolunteerThroughout the year we have been supported by a number of skilled volunteers who have each made a real difference to our ability to fund our clinical trials. In addition, supporters including cancer survivors and their families,

have generously come forward to share their stories, which assists us to raise awareness of the often hidden GI cancers and promote the difference our clinical trials are making to the lives of patients.Community support is vital in funding GI Cancer clinical trials research now and in the future. For more information on how to join us in the fight and get involved please contact us on 1300 666 769 or visit www.gicancer.org.au/getinvolved

Pictured Left:Gutsy Challenge team standing at the top of the highest mountain in the Southern Hemisphere – Mt Aconcagua Pictured (Top L-R):1. Catherine Trevaskis & Ngaire Parkyn - Larapinta

Gutsy Challenge Adventure 2. Sophia Hamblin Wang & Nik Wansbrough-

200km Run for Research Gutsy Challenge3. Dr Lorraine Chantrill, AGITG Director leading the

Larapinta Gutsy Challenge4. Club Industry Gutsy Golf Day participants5. Kate Holberton & partner Gary – Sugar

Free Gutsy Challenge for Pancreatic Cancer Awareness Month

6. Winning Team from the Dominic Colagiuri Memorial Cup

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Thank you to our members who give their time, expertise and commitment freely, to our sponsors who support our activities financially, and to our donors who give generously to continue to change medical practice in Australasia and throughout the world. We could not continue our important work without your support.

GI Cancer Institute Sponsors

Platinum Sponsors

Gold Sponsor

THANK YOU

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Australasian Gastro-Intestinal Trials Group & GI Cancer Institute · ABN 34 093 854 267Locked Bag M250, Camperdown NSW 2050 · T. 1300 666 769 · F. 02 9562 5348

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