RECENT TRENDS IN RECENT TRENDS IN CLINICAL RESEARCHCLINICAL RESEARCH

DR. CHANCHAL GOSWAMIDR. CHANCHAL GOSWAMI

Medical DirectorMedical Director

B.P. Poddar Hospital & Medical Research Ltd.B.P. Poddar Hospital & Medical Research Ltd.

WHY CLINICAL TRIALS??WHY CLINICAL TRIALS??

Clinical trials are experiments to determine the Clinical trials are experiments to determine the value of treatments. value of treatments.

Present day principles of treatment – no more Present day principles of treatment – no more based on “GUT FEELING” or “PERSONAL based on “GUT FEELING” or “PERSONAL EXPERIENCE” EXPERIENCE”

Practically, every single modality of treatment Practically, every single modality of treatment in every speciality today – based on in every speciality today – based on “EVIDENCE BASED MEDICINE”. “EVIDENCE BASED MEDICINE”.

Clinical Trials are needed to generate Clinical Trials are needed to generate ‘EVIDENCE”‘EVIDENCE”

LEVELS OF EVIDENCE IN LEVELS OF EVIDENCE IN MEDICINEMEDICINE::

Level ILevel I: Evidence obtained from at : Evidence obtained from at

least one properly designed least one properly designed

randomized controlled trial. randomized controlled trial.

Level II:Level II: Evidence obtained from Evidence obtained from well designed controlled trials well designed controlled trials without randomization.without randomization.

Level III:Level III: Opinions of respected Opinions of respected authorities, based on clinical authorities, based on clinical experience, descriptive studies, or experience, descriptive studies, or reports of expert committees.reports of expert committees.

Overview of Clinical Trials in IndiaOverview of Clinical Trials in India

Total Investment in Clinical Trials in Total Investment in Clinical Trials in India (McKinsey’s estimates):India (McKinsey’s estimates):In 2002 – $ 70 millionIn 2002 – $ 70 million

Future ProjectionsFuture ProjectionsBy 2007 - about $ 200 millionBy 2007 - about $ 200 millionBy 2010 - about $ 1 billion. By 2010 - about $ 1 billion.

Why India as a Destination for Why India as a Destination for Clinical Trials. Clinical Trials.

Huge population suffering from a vast Huge population suffering from a vast no. of various diseases, i.e. a High no. of various diseases, i.e. a High Disease LoadDisease Load

??Less Stringent Rules and Regulations ??Less Stringent Rules and Regulations + about 60 – 70% cheaper compared to + about 60 – 70% cheaper compared to Western Countries to conduct a trial. Western Countries to conduct a trial.

About 200 – 250 investigators already About 200 – 250 investigators already well trained in Good Clinical Practice.well trained in Good Clinical Practice.

Nearly 150 hospitals have adequate Nearly 150 hospitals have adequate infrastructure to conduct clinical trials.infrastructure to conduct clinical trials.

Availability of English speaking, well Availability of English speaking, well trained man power to conduct the trials. trained man power to conduct the trials.

PITFALLS OF A CLINICAL PITFALLS OF A CLINICAL TRIALTRIAL

Human “GUINEAPIGS”????Human “GUINEAPIGS”???? Medical COLONIALISM ???Medical COLONIALISM ???

Phases of a Clinical Trial Phases of a Clinical Trial

Phase I TrialsPhase I Trials – Earliest trials in the life – Earliest trials in the life of a new drug/treatment.of a new drug/treatment.

Done to find out:Done to find out:a. The Safe dose rangea. The Safe dose rangeb. The Side Effectb. The Side Effectc. How the body copes with the drugc. How the body copes with the drugd. If the treatment has its desired effects. d. If the treatment has its desired effects.

Phase II Trials:Phase II Trials: Are done to find out:Are done to find out:a. If the new treatment works well enougha. If the new treatment works well enough to be sent to Phase 3 to be sent to Phase 3b. Which types of cancer is it effective b. Which types of cancer is it effective

againstagainstc. More about side effects & their c. More about side effects & their

managementmanagementd. More about the most effective dose to d. More about the most effective dose to

useuse

Phase III TrialsPhase III Trials : : Usually compare new treatment Usually compare new treatment with the current standard treatmentwith the current standard treatment

May compare:May compare:a. A completely new treatment with a. A completely new treatment with

standard treatmentstandard treatmentb. Different doses/ways of giving a standardb. Different doses/ways of giving a standard treatment treatmentc. A new radiotherapy schedule with ac. A new radiotherapy schedule with a standard one. standard one.

Phase IV Trials:Phase IV Trials: Done after a drug has Done after a drug has been shown to work & granted a licence. been shown to work & granted a licence.

Objective:Objective: To find out To find outa. More about side effects & safetya. More about side effects & safetyb. Long term risks and benefitsb. Long term risks and benefitsc. How well the drug works when it’s c. How well the drug works when it’s

used more widely than in clinical trials. used more widely than in clinical trials.

PREREQUISITES OF A PREREQUISITES OF A CLINICAL STUDYCLINICAL STUDY

Feasibility Feasibility Medico-legal and Ethical Issues.Medico-legal and Ethical Issues. Appraisal of Clinical Efficacy and Safety Appraisal of Clinical Efficacy and Safety Approval by the Ethics Committee Approval by the Ethics Committee

BASIC PLAN OF ALL BASIC PLAN OF ALL STUDIESSTUDIES

INFORMED CONSENT + FULL APPRAISAL OF THE INFORMED CONSENT + FULL APPRAISAL OF THE PATIENTS AND THEIR RELATIVES REGARDING PATIENTS AND THEIR RELATIVES REGARDING THE STUDYTHE STUDY

INCLUSION AND EXCLUSION CRITERIA INCLUSION AND EXCLUSION CRITERIA EVALUATIONEVALUATION

SCREENING TEST & BASELINE EVALUATION – SCREENING TEST & BASELINE EVALUATION – CLINICAL, BIOCHEMICAL, RADIOLOGICALCLINICAL, BIOCHEMICAL, RADIOLOGICAL

DRUG ADMINISTRATIONDRUG ADMINISTRATION

PERIODIC ASSESSMENT PERIODIC ASSESSMENT

COMPLETED CLINICAL COMPLETED CLINICAL STUDIES : 1STUDIES : 1

““A Multicenter, Phase II Study ofA Multicenter, Phase II Study of

Cremophor Free, Polymeric, Cremophor Free, Polymeric,

Nanoparticle Formulation of Nanoparticle Formulation of

Paclitaxel (DO/NDR/02) in locally Paclitaxel (DO/NDR/02) in locally

advanced and Metastatic Breastadvanced and Metastatic Breast

Cancer” Cancer”

COMPLETED CLINICAL STUDIES : 2COMPLETED CLINICAL STUDIES : 2““A Multi-Centric, Open Label, Phase-A Multi-Centric, Open Label, Phase-

III clinical trial to evaluate the safetyIII clinical trial to evaluate the safety

and efficacy of recombinantand efficacy of recombinant

interleukin-2 in patients with metastaticinterleukin-2 in patients with metastatic

renal cell carcinoma, followed up to 6renal cell carcinoma, followed up to 6

months for survival”months for survival”

ON-GOING STUDY - 1ON-GOING STUDY - 1 A Multicentric Phase III Study to evaluate A Multicentric Phase III Study to evaluate

“Palonosetron and Ondansetron in “Palonosetron and Ondansetron in chemotherapy induced nausea and chemotherapy induced nausea and vomiting”. vomiting”.

Objective: To assess and compare the safetyObjective: To assess and compare the safetyand efficacy of Palonosetron and and efficacy of Palonosetron and Ondansetron in moderately emetogenic Ondansetron in moderately emetogenic chemotherapy. chemotherapy.

ON GOING STUDY – 2 ON GOING STUDY – 2 A RANDOMISED, DOUBLE-BLIND, PARALLELA RANDOMISED, DOUBLE-BLIND, PARALLEL

GROUP, MULTICENTRE PHASE III STUDYGROUP, MULTICENTRE PHASE III STUDY

COMPARING THE EFFICACY & TOLERABILITYCOMPARING THE EFFICACY & TOLERABILITY

OF FULVESTRANT (FASLODEXOF FULVESTRANT (FASLODEXTMTM) 500mg WITH) 500mg WITH

FULVESTRANT (FASLODEXFULVESTRANT (FASLODEXTMTM) 250 mg IN POST) 250 mg IN POST

MENOPAUSAL WOMEN WITH ESTROGENMENOPAUSAL WOMEN WITH ESTROGEN

RECEPTOR POSITIVE ADVANCED BREAST RECEPTOR POSITIVE ADVANCED BREAST

CANCER PROGRESSING OR RELAPSING AFTERCANCER PROGRESSING OR RELAPSING AFTER

PREVIOUS ENDOCRINE THERAPYPREVIOUS ENDOCRINE THERAPY

ONGOING STUDY - 3ONGOING STUDY - 3

XM01-21 (PLATINUM CONTAINING XM01-21 (PLATINUM CONTAINING CHEMOTHERAPY / SOLID TUMOURS)CHEMOTHERAPY / SOLID TUMOURS) EFFICACY & SAFETY OF XM01 COMPARED EFFICACY & SAFETY OF XM01 COMPARED TO TO PLACEBO ANDPLACEBO AND EPOETIN BETAEPOETIN BETA IN IN PATIENTS WITH SOLID TUMOURS PATIENTS WITH SOLID TUMOURS RECEIVING PLATINUM-CONTAINING RECEIVING PLATINUM-CONTAINING CHEMOTHERAPY, A MULTINATIONAL, CHEMOTHERAPY, A MULTINATIONAL, MULTICENTRE, RANDOMISED, PLACEBO- MULTICENTRE, RANDOMISED, PLACEBO- AND ACTIVE-CONTROLLED, DOUBLE-AND ACTIVE-CONTROLLED, DOUBLE-BLIND, PARALLEL-GROUP PHASE III STUDYBLIND, PARALLEL-GROUP PHASE III STUDY

ONGOING STUDY - 4ONGOING STUDY - 4 XMO1-22XMO1-22 ((nonplatinum nonplatinum chemotherapy / solid tumours & chemotherapy / solid tumours &

non-myeloid non-myeloid haematological tumours) Efficacy & Safety of haematological tumours) Efficacy & Safety of

XMO1 compared to placeboXMO1 compared to placebo in patients with solid tumours in patients with solid tumours

or non-myeloid haematological tumours receiving non-or non-myeloid haematological tumours receiving non-

platinum chemotherapy, A multinational, multicentre, platinum chemotherapy, A multinational, multicentre,

randomised, placebo-controlled, double-blind, parallel-group randomised, placebo-controlled, double-blind, parallel-group

phase III study.phase III study.

ON-GOING STUDY - 5ON-GOING STUDY - 5

XMO1-23XMO1-23 (Haematologic Malignancies NHL, CLL, MM). (Haematologic Malignancies NHL, CLL, MM).

Efficacy and safety of Efficacy and safety of XMO1 compared toXMO1 compared to placeboplacebo in in

anaemic patients with low grade non-Hodgkin’s lymphoma, anaemic patients with low grade non-Hodgkin’s lymphoma,

chronic lymphocytic leukemia or multiple myeloma chronic lymphocytic leukemia or multiple myeloma

receiving anticancer therapy.receiving anticancer therapy.

A multinational, multicentre, randomised, placebo A multinational, multicentre, randomised, placebo

controlled, double-blind parallel-group phase III study.controlled, double-blind parallel-group phase III study.

UPCOMING STUDIES - 1UPCOMING STUDIES - 1

““AN OPEN-LABEL TWO ARM RANDOMIZED PHASE II AN OPEN-LABEL TWO ARM RANDOMIZED PHASE II

STUDY OF TWO DIFFERENT DOSING REGIMENS OF STUDY OF TWO DIFFERENT DOSING REGIMENS OF

CAPECITABINE IN COMBINATION WITH CAPECITABINE IN COMBINATION WITH

INTRAVENOUS DOCETAXEL (Q3W) IN PATIENTS INTRAVENOUS DOCETAXEL (Q3W) IN PATIENTS

WITH 1WITH 1STST LINE ANTHRACYCLINE FAILURE, LOCALLY LINE ANTHRACYCLINE FAILURE, LOCALLY

ADVANCED AND / OR METASTATIC BREAST CANCER”ADVANCED AND / OR METASTATIC BREAST CANCER”

UPCOMING STUDIES - 2UPCOMING STUDIES - 2

PHASE II, MULTICENTER, OPEN LABEL PHASE II, MULTICENTER, OPEN LABEL STUDY OF SLITSTUDY OF SLITTMTM (SUSTAINED RELEASE (SUSTAINED RELEASE LIPID INHALATION TARGETING) LIPID INHALATION TARGETING) CISPLATIN BY INHALATION IN THE CISPLATIN BY INHALATION IN THE TREATMENT OF PATIENTS WITH TREATMENT OF PATIENTS WITH BRONCHOALVEOLAR CARCINOMA BRONCHOALVEOLAR CARCINOMA (PROTOCOL NO.T01-202)(PROTOCOL NO.T01-202)

UPCOMING STUDIES: 3UPCOMING STUDIES: 3

““AN OPEN LABEL, COMPARATIVE, AN OPEN LABEL, COMPARATIVE,

RANDOMIZED, MULTICENTER STUDYRANDOMIZED, MULTICENTER STUDY

TO DETERMINE EFFICACY AND TO DETERMINE EFFICACY AND

SAFETY OF DRF7295 AND FOLFOX4 SAFETY OF DRF7295 AND FOLFOX4

COMBINATION AS FIRST LINE COMBINATION AS FIRST LINE

THERAPY IN PATIENTS WITH THERAPY IN PATIENTS WITH

LOCALLY ADVANCED AND / OR LOCALLY ADVANCED AND / OR

METASTATIC COLORECTAL CANCER”.METASTATIC COLORECTAL CANCER”.

UPCOMING STUDIES: 4UPCOMING STUDIES: 4

““A RANDOMIZED PHASE III STUDY OFA RANDOMIZED PHASE III STUDY OF

ALIMTA ALIMTA ® ® (PEMETREXED) AND(PEMETREXED) AND

CARBOPLATIN VERSUS ETOPOSIDE CARBOPLATIN VERSUS ETOPOSIDE

AND CARBOPLATIN IN EXTENSIVE-AND CARBOPLATIN IN EXTENSIVE-

STAGE SMALL CELL LUNG CANCER ”.STAGE SMALL CELL LUNG CANCER ”.

UPCOMING STUDIES: 5UPCOMING STUDIES: 5

A Multicenter, Randomized, Double Blind, A Multicenter, Randomized, Double Blind, Placebo- Controlled, Parallel- Arm Study of the Placebo- Controlled, Parallel- Arm Study of the Effect of Intravenous AVE0005 (VEGF Trap) Effect of Intravenous AVE0005 (VEGF Trap) Administered Every 2 weeks in Advanced Administered Every 2 weeks in Advanced Ovarian Cancer Patients with Recurrent Ovarian Cancer Patients with Recurrent Symptomatic Malignant Ascites.”Symptomatic Malignant Ascites.”

UPCOMING STUDIES: 6UPCOMING STUDIES: 6

A Randomized, Open Label Multi-center study A Randomized, Open Label Multi-center study of Single Agent Larotaxel (XRP9881) at 90 of Single Agent Larotaxel (XRP9881) at 90 mg/mmg/m22 every 3 weeks Compared to every 3 weeks Compared to Continuous Administration of 5-FU For the Continuous Administration of 5-FU For the Treatment of Patients with Advanced Treatment of Patients with Advanced Pancreatic Cancer Previously Treated With A Pancreatic Cancer Previously Treated With A Gemcitabine- Containing Regimen”.Gemcitabine- Containing Regimen”.

Clinical Research TeamClinical Research Team

InvestigatorsInvestigators Dr. Chanchal GoswamiDr. Chanchal Goswami Dr. Anil PoddarDr. Anil Poddar Dr. Litan Naha BiswasDr. Litan Naha Biswas Dr. Maitrayee Dr. Maitrayee

BhattacharyaBhattacharya Dr. Prasenjit ChatterjeeDr. Prasenjit Chatterjee Dr. Tapti SenDr. Tapti Sen

Study Co-ordinatorsStudy Co-ordinators Dr. Aniruddha BhattacharyaDr. Aniruddha Bhattacharya Dr. Piyush KediaDr. Piyush Kedia Dr. Srabani MittalDr. Srabani Mittal Dr. Bikas PalDr. Bikas Pal Dr. Koyel DasDr. Koyel Das

Clinical Research AssistantClinical Research Assistant : : Gargi RoychowdhuryGargi Roychowdhury

Medical Records InchargeMedical Records Incharge: : Anindya ChakrabortyAnindya Chakraborty

Librarian:Librarian: Partha Protim DasPartha Protim Das Study Nurse :Study Nurse : Purnima SenPurnima Sen