!\I. R. R. Hospital~

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# 3 & 3A, Hesaraghatta Main Road, Chikkasandra, Near Chikkabanavara Railway Station,

Letter of intimation of the d~CI§rohsl~~O:R'b?,:~~7/~~~~~tI\6p~sar37 4117

Date: 24-DEC-2011FromThe chairmanInstitutional Ethics Committee

NRR Hospital, 3 & 3A, Hesaraghatta main road,Chikkasandra, near Chikkabanabara railway station,Bangalore 560090.

ToDr. Yathish Kumar HM

Head, Department of OncologyNRR Hospital, 3 & 3A, Hesaraghatta main road, Chikkasandra,Near Chikkabanabara railway station, Bangalore - 560090

Dear Dr.Yathish Kumar H M

Sub: Intimation regarding the decision taken on your proposed research study 00102C00004

The research proposal titled"A Phase II, Randomized, Double-blind, Placebo-controlled, Multi-centre Study to Assess the Efficacyand Safety of AZD8931 In Combination with Anastrozole, Compared to Anastrozole alone, in Post-menopausal Women With Hormone Receptor-positive, Endocrine Therapy-naive, Locally-advanced orMetastatic Breast Cancer (MINT)".Documents submitted by you on 12-DEC-2011 were taken up for review in the meeting heldon 24-DEC-2011

The following documents were reviewed in the meeting.

1,. Clinical Study Protocol Edition number 1 dated 31 July 20092. Clinical Study Protocol, Administrative Change Number 1 Dated 20 Aug 20093. Clinical Study Protocol Amendment number 1, dated 8 March 20104. Clinical Study Protocol Amendment number 2, dated 4 May 20105. Clinical Study Protocol Local Amendment number 1, dated 14 Oct 20106. Clinical Study Protocol Amendment number 3, dated 18 Feb 20117. File Note for Quality of Life Questionnaires

8. File note 1 dated 03 Sep 2010 to Clinical Study Protocol, Edition Number 2 Dated 04 May 20109. Investigators Brochure Edition Number 6, Dated 29 March 201110. Adult Study Subject Information and Consent Forms: Language: English, Hindi and Kannada

• Master Version Number 4: Version Date 18 Feb 2011, India Version Number 2.0: India

Version Date 25 Feb 201111. Genetic Research Addendum to Informed consent Form: Language: English, Hindi and Kannada

• Master Version Number 2: Master Version Date 08 March 2010, India Version Number 1.0:India Version Date 23 June 2010

~":)

NRR N. R. R. Hospital~

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# 3 & 3A, HesaraghaHa Main Road, Chikkasandra, Near Chikkabanavara Railway Station,

Letter of in'TlW~If{aii58¥~~ ~~c1~i61,1~i~d~h6JnIYf\"e:fS~~1i'~lh1rfcip~\W7611.12. Quality of Life Questionnaire:

a. Language: English, FACT-B, FACT-ES& EQ-sD

b. Language: Kannada, FACT-B & EQ-sDc. Language: Hindi, FACT-B & EQ-5D

13. Study Participation Card:

a. Language: English, India Version 2.0: Dated 8 Sep 2011

b. Language: Kannada, India Version 2.0: Dated 8Sep 2011

c. Language: Hindi, India Version 2.0,: Dated 8 Sep 2011

14. RA Letters:

• DCGI Approval letter dated 27 September 2010

• Approval letter for Clinical Study Protocol Local Amendment, dated 15 November 2010

• Approval letter for Revised Clinical Study Protocol edition No.3, Clinical Study ProtocolAmendment NO.3 and Adult Informed Consent Form version (India) 2.0, dated 30 Mar 2011

• Import License dated 4 Jan 2011

• NOC for export License for Biological Sample (Blood), dated 27 sep 2011

• NOC for export-License for Biological Sample (Tumor Tissue samples), dated 16 sep 2011

15. Certificate of Liability Insurance (Policy period: February 01, 2011 to February 29, 2012)

16. Principal Investigator's Letter of Undertaking

17. Principal Investigator's Curriculum Vitae

18. Annotated e CRF-Version 17.2 dated 23 Apr 201019. File note 1 dated 29th Apr 2010 toAnnotated e CRF-Version 17.2 dated 23 Apr 2010

20. Final clinical study agreement

21. DCGI Acknowledgement letter Annual Status Report dated ls/DEC/2011

22. Blinded SUSAR line listings:

a. Blinded SUSAR line listings for Investigators, dated 26 Mar 2010 to 25 Sep 2010

b. Blinded SUSAR line listings for Investigators, dated 26 Sep 2010 to 25 Mar 2011

c. Blinded SUSAR line listings for Investigators, dated 26 Mar 2011 to 25 Sep 2011

After thoroughly scrutinizing the ethical and scientific aspects of the proposal, thecommittee has decided that the proposal may be approved in its presented form.

The IEC expects to be informed about the progress of the study, any SAE occurring in thecourse of the study, any changes in the protocol and patient information/informed consentand asks to be provided a copy of the final report or summary report.The IEC works on the concepts ICH-GCP and applicable regulatory requirement

Y~rffincerely

(\J~\'~Signature and date

(Dr.R.Shreenivasan)

Co- Chair-Person)I ,~:;'Stftl1tJona'EthICS Committee.. ,.;-, Hospital. Bangalore 560 090

~NRR N. R. R. Hospital

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# 3 & 3A, HesaraghaHa Main Road, Chikkasandra, Near Chikkabanavara Railway Station,letter of intffflMfOnSdP m~Bed~fo1rSt2iiteJfdftl'ffte f~~MJ~lh"tffl>~MMf27611.

Enclosures:1. The list of members who attended the meeting and participated in the review of the

proposal with their signatures2. Checklist evaluated while making decision on the research proposal

~NRR !\I. R. R. Hospital

~SERVE TO CURE

# 3 & 3A, Hescrcqhottc Main Road, Chikkasandra, Near Chikkabanavara Railway Station,

Letterof in\'lM~Yr&il58~~)\~ f(fe6~btJsl~~~\f'Jpj'Wef~~e1jll~Pop~F611.

Enclosure 1

The list of members who attended the meeting and participated in the review of the proposal withtheir signatures

..... .... . ...

Opinlon.about I

S.No Name Deslgnatlon ...• the proposal Signature Date(A/B/c)*

........Dr. Ramesh.R Chair-person h1 MD(Anesthesiology) '/ A. 1'"'1

Dr.R.Shreenivasan ViceChairperson '\11- " K-~,~ J~-\~-\\2 MBBS ClinicianDr. Priyadarshini. Pharmacologist,

A ~L L_/L L3 Bai.G ~JI0JU,11MD(Pharmacology) "0 - .~---Dr.Murali R Nadig Medical -A

~Jif /11 'lOlt4 MD(Nuclear Scientist

Medicine)Dr. V. Shrinivas Medical

4 -5 MD(Pathologist) ScientistDr.Ravi Kumar, MBBS, Clinician 1,\~ ~1 j2-) 1\6 DTCD, j)DNB(Pulmonologist) :-0'/Dr. P.G.Chandre Clinician

,,/

1/\7 Gowda, MBBS., MS --- r-I(E.N.T)Mrs. Veena .T.T. Social-

~~ ~4 J r2-/!)8 BA.MA.M-PHIL worker IEducati t~onalist

Mr. Kuldeep Singh BE Non Medical

\~~9 (Electronics and Scientist A :J-4t \2-ll\communication)

10Mr. S.M. Dayanand Legal expert -:.Il I~ ~y 11«.1 J IPatu, BA, llB, llMMrs. Sanjana Purohit layperson & rBA, PGDHRM Member f\ :2-~\ \~ \,

11Secretary

Remarks:

* Favourable in its presented form = A, not favourable in its presented form = B, suggestingchanges = C

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# 3 & 3A, HesaraghaHa Main Road, Chikkasandra, Near Chikkabanavara Railway Station,Letter of in¥WW~ltran'~'~~·fled~M#.\lia'lt~jI,6oY1lm~:f~~~1.\t1,~:p~~M27611.

Enclosure 2

Checklist evaluated while making decision on the research proposal

S.Criteria N/AP

No.Yes No

1Is the investigator qualified as per MCI norms and vexperienced to carry out the trial?

2Do the committee members have any conflict of interest in vthe proposed research?

3Is the investigator's CV attached with the proposal and is

/updated & signed?

4Is the proposal attached with informed consent documents

Vin English and vernacular languages?

5Does the study protocol contain all the relevant information

Vas per the regulatory requirements?

Basic information. The following are explained in the studyproposal in detail.

_~~_~_E!_~~~~~~~ripti~~ __~!_!~y~~!i~!i~_na IJ~~~~l!!=.!~ ..>.._ ..__ .._ ............... _---_ ...._ ....

Summary of non clinical studies likely to be significant on the vstudy proposal

6 Summary of known and potential risks and benefits if any for /'J!~!11a~~~~l~cts _ ----_ ............... __ ........ ------_ .............. _ .....

Description and explanation of dosage regimenand treatment period vStatement to the effect that the study will be conducted in

/'compliance with protocol, GCP and applicable regulatoryrequirements

7Study objectives - Detailed description of primary and ./secondary objectives

8 Is the study design ethically right and scientifically sound vSelection and withdrawal of subjects - the following arediscussed in the proposal

--_. ---------- ....._- ./'"9 Subjects inclusion criteria-- ./Subjects Exclusion criteria _.-

/'_?~_~L~~~s._~~!~~_~~~~~!j!~~~_________..._---_ ..._-_ •...-.__ ._.._ ......... __ ....__ .....- .....-._- ./'Study termination criteriaTreatment of subjects - Are the following addressed?Description of treatment to be administered V"""

Name (s) of all products J- . ----------"-_._-------_._l.?~~_~~~_~)of~~Lp.!.°d._~~!~__ ....-...-.-.- ....-~-....~...-.-...-...--.- ..--...-----.-~----------

./

10 Dosing schedule (s) /Administration route/mode (s)

../Treatment periods including follow-up of each subject part of Ja group or subgroup treated with the investigational productor participating to the study

~")NRR N. R. R. Hospital~

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letter 0 Ira~QJ~pQ~IItMQIII$5t,ame, CQAme~.~I'MiM'QMSat7611.

Efficacy parameters and assessmentDescription of efficacy parameters ........--'

11Procedures and timing to assess, record and analyze efficacy

parameters.../'

Safety assessment ---Description of safety parameters c-:

Procedures and timing to assess, record and analyze safety ../

12parametersProcedures to obtain reports of and record and signal ./'adverse events and intercurrent illnessesType and duration of follow-up of subjects after adverse /eventsStatistical planDescription of statistical methods to be used including any ./planned periodical

_cmalysis(ses) sch~~ule .. ...-Anticipated number of subjects for multi-centre studies, the V13 anticipated number ofsubjects for each site should be indieatedReasons for choice of sample size including comments (orcalculations) of the ./study power and clinical justificationSignificance level to be used -./'

The proposal has addressed all other issues such as quality14 assurance, ethics, informed consent, publication policy, V

compensation and insurance related issues15 Others ... specify v'

Remarks:

Evaluation done by: ~ ..e!f!;.h.'IJ;;,,).'(signature with date}

Name and designation:1)e - fl( 1't ADA1U \+tJJ,L 1&m· ~

f~"1J')'-LC>LDt;,UT .