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 Study
“A prospective, randomized, multi-centric clinical study to compare Trastuzumab (Test Product, Zydus) with Trastuzumab (Reference Product, Roche/Genentech ) in patients with metastatic breast cancer.â€
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
TRA.12.001.02.1, version 2.1 dated 18 Feb 2014
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Acharya Tulsi Regional Cancer Treatment & Research Institute
Acharya Tulsi Regional Cancer Treatment & Research Institute, Dept. Of Radiotherapy, P.B.M. Hospital Campus, S.P. Medical College,
Bikaner, Rajasthan 334003 Bikaner RAJASTHAN
Chittaranjan National Cancer Institute, Department of Oncology, 37,S.P.Mukherjee Road,Kolkata-700 026 P.O.: Kalighat, West Nengal, India Kolkata WEST BENGAL
Dr. GVN Cancer Institute, Dept. Of Oncology, No. 46, Singarathope, Trichy-62008, Tamil Nadu Tiruchirappalli TAMIL NADU
0431-2700712 0431-4010000 arunonco@gmail.com
Dr Kambale krishna Marotiro
Goverment Medical College and Hospital Nagpur
Goverment Medical College and Hospital Nagpur, Depoartment of Radiation Therapy, Goverment Medical College and Hospital Nagpur Nagpur MAHARASHTRA
9850246275
drkambleonco@gmail.com
Dr Murali Subramanian
Gurushree Hi-Tech Multi speicality Hopsital
Gurushree Hi-Tech Multi speicality Hopsital, Dept. of Oncology, No.1558 Opp. Chandra layout Bus Stand, Vijaynagar Bangalore Karnataka, India Bangalore KARNATAKA
080-23392641 080-23394781 muralis_14@yahoo.com
Dr Shibashish Bhattacharya
Health Point Hospital
Health Point Hospital, Department of Oncology, 21, Prannath Pandit Street, Opp. Lansdown Padmapukur, Kolkata-700 025, India Kolkata WEST BENGAL
IPGME&R AND SSKM , Dept. Of Radio Oncology, 244 AJC Bose Road, Kolkata- 700 020 West Bengal, India Kolkata WEST BENGAL
09874166240
siddharthabasu24@gmail.com
Dr Niraj Bhatt
Kailash Cancer Hospital and Research centre
Kailash Cancer Hospital and Research centre, Dept. of Oncology, Muni Seva Ashram, PO- Goraj- 391760, Tal. waghodia, Dist Vadodara Vadodara GUJARAT
9925581480
medonc12@gamil.com
Dr Mohan Chandra Pant
King Georges Medical University
King Georges Medical University, Medical University),Chowk, Lucknow, Uttar Pradesh, INDIA 226003 Lucknow UTTAR PRADESH
0522-2258672
anand.misra02@gmail.com
Dr Naresh Soni
Manu Hospital and Research Centre
Manu Hospital and Research Centre, Dept. of oncology, Jawahar Lal Nehru Marg, Malviya Nagar, Jaipur - 302017, Rajasthan Jaipur RAJASTHAN
0141-2292530 0141-2293800 nareshsoni@yahoo.com
Dr Mukta Srinivasulu
Mehdi Nawaz Jung Institute of Oncology and regional Cancer centre
Mehdi Nawaz Jung Institute of Oncology and regional Cancer centre, Dept. of Oncology, Red Hills Hyderabad-500004 Hyderabad ANDHRA PRADESH
040-22314063
muktasrinivasulu@yahoo.co.in
Dr Mukesh S
Mysore Medical College & Research Institute
Mysore Medical College & Research Institute, Department of Department of Radiation oncology, Irwin Road, Mysore, Karnataka-570 001, India Mysore KARNATAKA
0821-2520512
dalmuk1@hotmail.com
Dr Yathish Kumar
NRR Hospital
NRR Hospital, Department of Oncology, No.3 and 3A, Hesarghatta Main Road, Chikkasandra, Next to Janapriya Apartments, Near Chikkabanavara Railway Station, Bangalore 560 090 Bangalore KARNATAKA
08028374115 08028374117 dryathish@hotmail.com
Dr Asha Arjunan
Regional Cancer Centre
Regional Cancer Centre, Dept. of Oncology, Medical College Campus, Thiruvananthapuram 695011 Thiruvananthapuram KERALA
0471-2442541 0471-2447454 drashaarjun@gmail.com
Dr Gaurav Agrawal
Sanjay Gandhi Post Graduate Institute of Medical Sciences
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Dept. of Endocrinology & Brest Cancer, Rae Bareli Rd, Lucknow, Uttar Pradesh 226014 Lucknow UTTAR PRADESH
0522-2494160 05222668017 gaurav@sgpgi.ac.in
Dr Uttam Soni
Sita devi Hospital
Sita devi Hospital, Department of Oncology, 74, Shri Ram Colony, B/H Chambal Grid, Hawa Sadak , Jaipur Jaipur RAJASTHAN
01412211372 01412210734 soniuttam@hotmail.com
Dr Om prakash Sharma
SMS Medical College
Department of Radiotheraphy,SMS Medical College, Department of Oncology, Jaipur-302 004, Rajasthan, India Jaipur RAJASTHAN
01412502158 01412359313 dromsharma22@gmail.com
Dr Sudeep Gupta
Tata Memorial Hospital
Tata Memorial Hospital, Dept. Of Oncology, Dr. E Borges Road, Parel, Mumbai 400 012 India Mumbai (Suburban) MAHARASHTRA
09821298642
sudeepgupta04@gmail.com
Dr Unmesh Vidyadhar Takalkar
United CIIGMA Institute Medical Sciences Pvt. Ltd
United CIIGMA Institute Medical Sciences Pvt. Ltd, Dept. Oncology, Plot No. 6, 6, Survey no. 10, Shahaoorwadi, Dargah Road Aurangabad-431005 Aurangabad MAHARASHTRA
Dr. GVN Cancer Institute Institutional Ethics Committee, Trichy-Tamil Nadu
Submittted/Under Review
Ethic Committee Kodliker,Memorial Hospital & CHGMA Hospital, Aurangabad, Maharashtra, India
Submittted/Under Review
Ethics Committee of Mysore Medical College and Associated Hospitals, Mysore, Karnataka, India
Submittted/Under Review
Ethics Committee of S.M.S. Medical College and Attached Hospitals, Jaipur, Rajasthan, India
Submittted/Under Review
Ethics Committee, S.P Medical College & A.G Hospitals Ethics Committee, Bikaner INDIA
Submittted/Under Review
Health Point Ethics Committee, Kolkata- India
Approved
Human Ethics Committee, Thiruvananthapuram INDIA
Submittted/Under Review
Institutional Ethics committee for Research Involving Human subjects, IPGME&R and SSKM Hospital, Kolkata- West Bengal, India
Approved
Institutional Ethics Committee Manu Hospital & Research Centre, Jaipur
Approved
Institutional Ethics Committee NRR Hospital, Bangalore, INDIA
Submittted/Under Review
Institutional Ethics Committee of CNCI, Chittaranjan National Cancer Institute INDIA
Submittted/Under Review
Institutional Ethics Committee Vijaynagar Bangalore India
Submittted/Under Review
Institutional Ethics Committee, CBMR, Lucknow INDIA
Submittted/Under Review
Institutional Ethics Committee, Jaipur, Rajasthan. India
Submittted/Under Review
Institutional Ethics Committee, King George s Medical College, Lucknow, INDIA
Submittted/Under Review
Institutional Ethics Committee, Mehdi Nawaz Jung Institute of Oncology and Regional Cancer Centre, Hyderabad
Submittted/Under Review
Institutional Ethics Committee, Sita devi Hospital, Jaipur, INDIA
Approved
Institutional Ethics Committee, TATA Memorial Hospital, , Mumbai Maharashtra, India
Submittted/Under Review
Kailash Cancer and Medical Centre Institutional Ethics Committee, Vadodra, India
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
Patients with metastatic breast cancer,
Intervention / Comparator Agent
Type
Name
Details
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.
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.
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.
ExclusionCriteria
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 Random Sequence
Computer generated randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To compare the single dose truncated pharmacokinetics (Cmax, AUC0-168hrs) of Trastuzumab (Zydus) as
compared to Herceptin (Reference) upto Day 7, both in combination with Paclitaxel in patients with
Metastatic Breast Cancer.
Day 1, Cycle 1 - Before the study drug administration i.e. 0 minutes, end of study drug administration (i.e. after 1.5 hours (end of infusion) ±15 minutes, after 3 hours ±15 minutes, after 4.5 hours ±15 minutes and after 6 hours ±15 minutes)
Day 7 - (168 hours ± 24 hours)
Day 14 - Optional - (336 hours ± 24 hours)
Day 1, Cycle2 ± 2 days
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) – Sum of Complete response (CR) and partial response at end of study and to compare the pharmacokinetics (Cmax, AUC0-last) and immunogenicity
At the End of study (21 days after last dose). i.e.
After 3 months.
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"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
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.