Clinical Trial Details (PDF Generation Date :- Tue, 22 Jun 2021 18

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Clinical Trial Details (PDF Generation Date :- Thu, 30 Sep 2021 03:42:49 GMT)

CTRI Number CTRI/2014/05/004605 [Registered on: 19/05/2014] - Trial Registered Prospectively Last Modified On 05/02/2015 Post Graduate Thesis No Type of Trial Interventional Type of Study Drug Study Design Randomized, Parallel Group Trial Public Title of Study A clinical trial intended to compare two formulations of Trastuzumab, tablets in patients with metastatic breast cancer. Scientific Title of “A prospective, randomized, multi-centric clinical study to compare Trastuzumab (Test Product, Study Zydus) with Trastuzumab (Reference Product, Roche/Genentech ) in patients with metastatic breast cancer.” Secondary IDs if Any Secondary ID Identifier TRA.12.001.02.1, version 2.1 dated 18 Feb 2014 Protocol Number Details of Principal Details of Principal Investigator Investigator or overall Name Dr Charu Gautam Trial Coordinator (multi-center study) Designation Associate VP – Global Clinical Operation Affiliation Cliantha Research Limited Address Sigma-1 Corporate, Off S.G.Highway, Bodakdev, Ahmedabad, Gujarat. Cliantha House, Opp. Pushparaj Tower,Near Judges Bungalow Road, Bodakdev Ahmadabad GUJARAT 380054 India Phone 07966135655 Fax 07966135641 Email [email protected] Details Contact Details Contact Person (Scientific Query) Person (Scientific Name Dr Charu Gautam Query) Designation Associate VP – Global Clinical Operation Affiliation Cliantha Research Limited Address Sigma-1 Corporate, Off S.G.Highway, Bodakdev, Ahmedabad, Gujarat. Cliantha House, Opp. Pushparaj Tower,Near Judges Bungalow Road, Bodakdev Ahmadabad GUJARAT 380054 India Phone 07966135655 Fax 07966135641 Email [email protected] Details Contact Details Contact Person (Public Query) Person (Public Query) Name Dr Chirag Shah Designation Head- Clinical Trials Affiliation Cliantha Research Limited Address Sigma-1 Corporate, Off S.G.Highway, Bodakdev, Ahmedabad, Gujarat. Cliantha House, Opp. Pushparaj Tower,Near Judges Bungalow Road, Bodakdev Ahmadabad

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GUJARAT 380054 India Phone 07966135631 Fax 07966135641 Email [email protected] Source of Monetary or Source of Monetary or Material Support Material Support > Sponsor: Cadila Healthcare limited Primary Sponsor Primary Sponsor Details Name Cadila Healthcare limited Address Sarkhej – Bavla N.H. No.8A, Moraiya, Tal: Sanand, Dist: Ahmedabad – 382 210, Gujarat, India Type of Sponsor Pharmaceutical industry-Indian Details of Secondary Name Address Sponsor NIL NIL Countries of List of Countries Recruitment India Sites of Study Name of Principal Name of Site Site Address Phone/Fax/Email Investigator Dr Ajay Sharma Acharya Tulsi Regional Acharya Tulsi Regional 0151-2226304 Cancer Treatment & Cancer Treatment & 0151-2226329 Research Institute Research Institute, drajaysharma55@gmail Dept. Of Radiotherapy, .com P.B.M. Hospital Campus, S.P. Medical College, Bikaner, Rajasthan 334003 Bikaner RAJASTHAN Dr Kalyan Kusum Chittaranjan National Chittaranjan National 033-24765101 Mukherjee Cancer Institute Cancer Institute, 033-24757606 Department of kkmukharjee4u@hotma Oncology, il.com 37,S.P.Mukherjee Road,Kolkata-700 026 P.O.: Kalighat, West Nengal, India Kolkata WEST BENGAL Dr Arun Seshachalam Dr. GVN Cancer Dr. GVN Cancer 0431-2700712 Institute Institute, Dept. Of 0431-4010000 Oncology, No. 46, [email protected] Singarathope, Trichy-62008, Tamil Nadu Tiruchirappalli TAMIL NADU Dr Kambale krishna Goverment Medical Goverment Medical 9850246275 Marotiro College and Hospital College and Hospital Nagpur Nagpur, Depoartment [email protected] of Radiation Therapy, om Goverment Medical College and Hospital Nagpur Nagpur

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MAHARASHTRA Dr Murali Subramanian Gurushree Hi-Tech Gurushree Hi-Tech 080-23392641 Multi speicality Hopsital Multi speicality Hopsital, 080-23394781 Dept. of Oncology, [email protected] No.1558 Opp. Chandra m layout Bus Stand, Vijaynagar Bangalore Karnataka, India Bangalore KARNATAKA Dr Shibashish Health Point Hospital Health Point Hospital, 033-30575700 Bhattacharya Department of 033-24559037 Oncology, 21, Prannath shibashishbhattacharya Pandit Street, Opp. @ymail.com Lansdown Padmapukur, Kolkata-700 025, India Kolkata WEST BENGAL Dr Siddhartha Basu IPGME&R AND SSKM IPGME&R AND SSKM , 09874166240 Dept. Of Radio Oncology, 244 AJC siddharthabasu24@gm Bose Road, Kolkata- ail.com 700 020 West Bengal, India Kolkata WEST BENGAL Dr Niraj Bhatt Kailash Cancer Hospital Kailash Cancer Hospital 9925581480 and Research centre and Research centre, Dept. of Oncology, [email protected] Muni Seva Ashram, PO- Goraj- 391760, Tal. waghodia, Dist Vadodara Vadodara GUJARAT Dr Mohan Chandra King Georges Medical King Georges Medical 0522-2258672 Pant University University, Medical University),Chowk, anand.misra02@gmail. Lucknow, Uttar com Pradesh, INDIA 226003 Lucknow UTTAR PRADESH Dr Naresh Soni Manu Hospital and Manu Hospital and 0141-2292530 Research Centre Research Centre, Dept. 0141-2293800 of oncology, Jawahar [email protected] Lal Nehru Marg, m Malviya Nagar, Jaipur - 302017, Rajasthan Jaipur RAJASTHAN Dr Mukta Srinivasulu Mehdi Nawaz Jung Mehdi Nawaz Jung 040-22314063 Institute of Oncology Institute of Oncology and regional Cancer and regional Cancer muktasrinivasulu@yaho centre centre, Dept. of o.co.in Oncology, Red Hills Hyderabad-500004 Hyderabad ANDHRA PRADESH

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Dr Mukesh S Mysore Medical College Mysore Medical College 0821-2520512 & Research Institute & Research Institute, Department of [email protected] Department of Radiation oncology, Irwin Road, Mysore, Karnataka-570 001, India Mysore KARNATAKA Dr Yathish Kumar NRR Hospital NRR Hospital, 08028374115 Department of 08028374117 Oncology, No.3 and 3A, [email protected] Hesarghatta Main Road, Chikkasandra, Next to Janapriya Apartments, Near Chikkabanavara Railway Station, Bangalore 560 090 Bangalore KARNATAKA Dr Asha Arjunan Regional Cancer Regional Cancer 0471-2442541 Centre Centre, Dept. of 0471-2447454 Oncology, Medical [email protected] College Campus, m Thiruvananthapuram 695011 Thiruvananthapuram KERALA Dr Gaurav Agrawal Sanjay Gandhi Post Sanjay Gandhi Post 0522-2494160 Graduate Institute of Graduate Institute of 05222668017 Medical Sciences Medical Sciences, [email protected] Dept. of Endocrinology & Brest Cancer, Rae Bareli Rd, Lucknow, Uttar Pradesh 226014 Lucknow UTTAR PRADESH Dr Uttam Soni Sita devi Hospital Sita devi Hospital, 01412211372 Department of 01412210734 Oncology, 74, Shri Ram [email protected] Colony, B/H Chambal m Grid, Hawa Sadak , Jaipur Jaipur RAJASTHAN Dr Om prakash Sharma SMS Medical College Department of 01412502158 Radiotheraphy,SMS 01412359313 Medical College, dromsharma22@gmail. Department of com Oncology, Jaipur-302 004, Rajasthan, India Jaipur RAJASTHAN Dr Sudeep Gupta Tata Memorial Hospital Tata Memorial Hospital, 09821298642 Dept. Of Oncology, Dr. E Borges Road, Parel, sudeepgupta04@gmail. Mumbai 400 012 India com

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Mumbai (Suburban) MAHARASHTRA Dr Unmesh Vidyadhar United CIIGMA Institute United CIIGMA Institute 9822042425 Takalkar Medical Sciences Pvt. Medical Sciences Pvt. Ltd Ltd, Dept. Oncology, takalkar.unmesh@gmai Plot No. 6, 6, Survey l.com no. 10, Shahaoorwadi, Dargah Road Aurangabad-431005 Aurangabad MAHARASHTRA Details of Ethics Name of Committee Approval Status Date of Approval Is Independent Ethics Committee Committee? CIMS Ethics Approved 09/08/2014 No Committee- Dr. C. Desai Dr. GVN Cancer Submittted/Under No Date Specified No Institute Institutional Review Ethics Committee, Trichy-Tamil Nadu Ethic Committee Submittted/Under No Date Specified No Kodliker,Memorial Review Hospital & CHGMA Hospital, Aurangabad, Maharashtra, India Ethics Committee of Submittted/Under No Date Specified No Mysore Medical College Review and Associated Hospitals, Mysore, Karnataka, India Ethics Committee of Submittted/Under No Date Specified No S.M.S. Medical College Review and Attached Hospitals, Jaipur, Rajasthan, India Ethics Committee, S.P Submittted/Under No Date Specified No Medical College & A.G Review Hospitals Ethics Committee, Bikaner INDIA Health Point Ethics Approved 09/04/2014 No Committee, Kolkata- India Human Ethics Submittted/Under No Date Specified No Committee, Review Thiruvananthapuram INDIA Institutional Ethics Approved 16/04/2014 No committee for Research Involving Human subjects, IPGME&R and SSKM Hospital, Kolkata- West Bengal, India Institutional Ethics Approved 29/03/2014 No Committee Manu Hospital & Research Centre, Jaipur

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Institutional Ethics Submittted/Under No Date Specified No Committee NRR Review Hospital, Bangalore, INDIA Institutional Ethics Submittted/Under No Date Specified No Committee of CNCI, Review Chittaranjan National Cancer Institute INDIA Institutional Ethics Submittted/Under No Date Specified No Committee Vijaynagar Review Bangalore India Institutional Ethics Submittted/Under No Date Specified No Committee, CBMR, Review Lucknow INDIA Institutional Ethics Submittted/Under No Date Specified No Committee, Jaipur, Review Rajasthan. India Institutional Ethics Submittted/Under No Date Specified No Committee, King Review George s Medical College, Lucknow, INDIA Institutional Ethics Submittted/Under No Date Specified No Committee, Mehdi Review Nawaz Jung Institute of Oncology and Regional Cancer Centre, Hyderabad Institutional Ethics Approved 20/04/2014 No Committee, Sita devi Hospital, Jaipur, INDIA Institutional Ethics Submittted/Under No Date Specified No Committee, TATA Review Memorial Hospital, , Mumbai Maharashtra, India Kailash Cancer and Submittted/Under No Date Specified No Medical Centre Review Institutional Ethics Committee, Vadodra, India Regulatory Clearance Status Date Status from DCGI Approved/Obtained 10/03/2014 Health Condition / Health Type Condition Problems Studied Patients Patients with metastatic breast cancer Intervention / Type Name Details Comparator Agent Intervention Trastuzumab (Zydus) Trastuzumab will be administered in combination with paclitaxel, at an initial dose of 8 mg/kg as a 90 minute intravenous infusion followed by subsequent once every three weeks, dose of 6 mg/kg i.v 30-90 minute intravenous infusions.Total durationof therapy is approx 3 months.

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Comparator Agent Herceptin (Roche/Genentech) Herceptin will be administered in combination with paclitaxel, and Loading dose of 8 mg/kg over 90 min on day 1 followed by 6 mg/kg over 30-90 min every 3 weekly maintenance dose.Total duration of therapy is approx 3 months. Inclusion Criteria Inclusion Criteria Age From 18.00 Year(s) Age To 80.00 Year(s) Gender Female Details 1. Patients with histologically or cytologically confirmed uni-dimensionally measurable metastatic breast cancer.

2. Have a strong Her-2 over-expression as described by a 3+

3. Patients with ECOG performance status 0-2. Exclusion Criteria Exclusion Criteria Details 1. Newly diagnosed metastatic breast cancer patients other than HER2 +ve patients. (Note since there is no treatment other than Trastuzumab for HER2+ve MBC such patients will not be excluded)

2. Have a history of congestive heart failure (CHF)

3. Have an abnormal LVEF

4. History of myocardial infarction within 6 months before randomization.

5. Have severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.

6. Have had prior mediastinal irradiation (except internal mammary-node irradiation for the present breast cancer).

7. Have a history of hypersensitivity to the Trastuzumab or to drugs with similar chemical structures, or to any of the excipients, or to murine proteins.

8. Have any concurrent disease or condition that, in the opinion of the investigator, would make the patient unsuitable for participation in the study. Method of Generating Computer generated randomization Random Sequence Method of An Open list of random numbers Concealment Blinding/Masking Open Label Primary Outcome Outcome Timepoints To compare the single dose truncated Day 1, Cycle 1 - Before the study drug pharmacokinetics (Cmax, AUC0-168hrs) of administration i.e. 0 minutes, end of study drug Trastuzumab (Zydus) as administration (i.e. after 1.5 hours (end of compared to Herceptin (Reference) upto Day 7, infusion) ±15 minutes, after 3 hours ±15 minutes, both in combination with Paclitaxel in patients after 4.5 hours ±15 minutes and after 6 hours with ±15 minutes) Metastatic Breast Cancer. Day 7 - (168 hours ± 24 hours) Day 14 - Optional - (336 hours ± 24 hours) Day 1, Cycle2 ± 2 days

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Day 1, Cycle 3 ± 2 days Day 1, Cycle 4 ± 2 days Day 21 after cycle 4 ± 7 days Secondary Outcome Outcome Timepoints To compare Objective Response Rate (ORR) – At the End of study (21 days after last dose). i.e. Sum of Complete response (CR) and partial After 3 months. response at end of study and to compare the pharmacokinetics (Cmax, AUC0-last) and immunogenicity Target Sample Size Total Sample Size=102 Sample Size from India=102 Final Enrollment numbers achieved (Total)=Applicable only for Completed/Terminated trials Final Enrollment numbers achieved (India)=Applicable only for Completed/Terminated trials Phase of Trial Phase 3 Date of First 26/05/2014 Enrollment (India) Date of First No Date Specified Enrollment (Global) Estimated Duration of Years=1 Trial Months=0 Days=0 Recruitment Status of Not Applicable Trial (Global) Recruitment Status of Closed to Recruitment of Participants Trial (India) Publication Details None Yet Brief Summary The purpose of this study is to determine the Pharmacokinetics, Safety, tolerability and efficacy of Trastuzumab (test, Zydus) as compared to Herceptin (Reference Product, Roche/Genentech), both in combination with Paclitaxel in patients with Metastatic Breast Cancer. The proposed subjects will be randomly assigned in a 2:1 ratio to Trastuzumab (Zydus - Test) and Trastuzumab (Reference). The computer generated randomization scheme will use blocks of 3 to maintain randomization balance. This study will be initiated only after obtaining the approvals of Institutional/ Independent Ethics Committee (IEC), clinical trial permission from the Drug Controller General of India (DCGI). The subjects qualifying inclusion and exclusion criteria will be invited to participate in this study. The recruitment will happen as per randomization schedule. Randomization list will be generated by computer generated randomization number. Randomization concealment will be achieved by the use of temper proof sealed opaque envelopes. The study will be an open label study. All the Response assessment for the enrolled patients will be based on RECIST Criteria Version 1.1. The study will be conducted in 5 patients to determine the infusion toxicities. These patients will be reviewed by the DSMB. If there are no clinically significant or higher incidences of infusion reactions, the participants will continue to receive the therapy and complete the 4 cycles as per the protocol. On completion of review of single cycle of infusion toxicity of 5 subjects, further randomization of the study will be initiated.

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