CTRI/2018/07/014881 [Registered on: 16/07/2018] Trial Registered Prospectively
Last Modified On:
08/04/2020
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
Safety and efficacy Assessment of Trastuzumab emtansine of Cadila Healthcare Ltd in comparison with Reference drug(Trastuzumab emtansine) for the treatment of metastatic breast cancer
A Prospective, Randomized, Multicenter, Comparative, Openlabel,
Parallel study to evaluate the Efficacy, Safety and
Pharmacokinetics of Test-Trastuzumab Emtansine (ZRC-
3256;Cadila Healthcare Ltd) and Reference-Trastuzumab
Emtansine(Kadcyla®, a product of Roche) in
HER2- Positive Metastatic Breast Cancer Patients.
HCG Manavata Cancer Centre Behind Shivang Auto, Mumbai Naka, Nashik-422001 Maharashtra, India. Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr Ajay Gogia
All India Institute of Medical Sciences (AIIMS)
Department of Medical Oncology, Dr. B.R.A, I.R.C.H,
All India Institute of Medical Sciences (AIIMS)
Ansari Nagar, New Delhi, 110029
New Delhi DELHI
9013000642
ajaygogia@gmail.com
Dr K Pavithran
Amrita Institute of Medical Sciences
Amrita Institute of Medical Sciences, AIMS Ponekkara P O Kochi- 682041 Kerala, India
Ernakulam KERALA
9895367090
drkpavithran@hotmail.com
Dr Tarachand Gupta
Apex Hospital Pvt. Ltd
SP 4& 6 MIA Malviya Nagar near apex circle,
Jaipur-302017 Jaipur RAJASTHAN
9819081403
tarachandg@gmail.com
Dr Kunjahari Medhi
Batra Cancer Centre
Department of Medical Oncology, Batra Cancer Centre, Batra Hospital and Medical Research Centre-1,Tughlakabad Institutional Area, Mehrauli Badarpur Road, New Delhi-110062 New Delhi DELHI
9818884856
medhiaiims@gmail.com
Dr Naresh Somani
Bhagwan Mahaveer Cancer Hospital & Research Centre
Consultant Medical Oncologist
Manipal Hospital
98, HAL Airport Road, Bangalore
Pin code – 560017
India
Bangalore KARNATAKA
9945687185
poonam.patil@manipalhospitals.com
Dr Mukhta Srinivasulu
MNJ Institute of oncology and Regional cancer Centre
"Dr. Mukhta Srinivasulu MNJ Institute of oncology and Regional cancer Centre
Lead-Clinical Research Coordinator,
Beside Niloufer Hospital, Redhills, Lakadikapul, Hyderabad, Telangana India-500004
Hyderabad TELANGANA
No. 54, Dr. Sankaran Road,
Namakkal – 637001, Tamilnadu, India
Namakkal TAMIL NADU
9819151554
bhaveshpoladia@gmail.com
Dr Tanveer Maksud
Unique Hospital- Multispeciality & Research Institute
"Unique Hospital- Multispeciality & Research Institute
Opp. Kiran Motor, Nr. Canal, Civil Hospital Char Rasta- Sosyo Circle Lane, Off Ring Road, Surat- 395002, Gujarat, India. Surat GUJARAT
"Institutional Ethics Committee Amrita Institute of Medical Sciences AIMS Ponekkara, P O Kochi - 682041 Kerala, India
Approved
"Institutional Ethics Committee Kailash Cancer Hospital and Research Center Goraj-391760. Waghodia, Vadodara, Gujarat, India"
Approved
"Manavata Clinical Research Institute Ethics Committee Curie Manavata Cancer Centre Opp Mahamarg Bus Stand, Mumbai Naka Nashik , 422004. Maharashtra, India."
Approved
Bhakti Vedanta Hospital Ethics CommitteeBhakti Vedanta Hospital Ethics Committee Bhakti Vedanta HEC Office, 6th Floor, Bhakti Vedanta Hospital & Research Institute, Srishti Complex, Bhakti Vedanta Swami Marg, Mira Road, East. Thane-401107 Maharashtra India
Approved
Department of Laboratory Medicine, Batra Hospital & Medical Research, Centre, 1, Tuglakabad Institutional Area, M. B. Road New Delhi 110062
Approved
Drug Trial Ethics Committee, Dayanand medical college & Hospital Tagore Nagar, Civil Lines Ludhiana -141001 Punjab India
Approved
Ethics committee of Manipal Hospitals, Manipal Hospitals, 98, HAL Airport Road, Bangalore - 560017
Approved
Ethics Committee Sanjeevani Cancer Hospital In Front of Jain Mandir Dawada Colony, Pachpedhi Naka, Raipur- 492001 Chhattisgarh
Approved
Ethics Committee Unique Hospital- Multispecialty & Research Institute Opp. Kiran Motor, Nr. Canal, Civil Hospital Char Rasta- Sosyo Circle Lane, Off Ring Road, Surat- 395002, Gujarat, India.
Approved
Ethics Committee, All India Institue of Medical Sciences, Room No 102, 1st Floor, Old O.T Block, Ansari Nagar, New Delhi-110029
Submittted/Under Review
Ethics Committee, S.P. Medical College & AG of Hospitals HRM Cardiovascular Science & Research Bikaner 334003, Rajasthan
Approved
GVN Institutional Ethics Committee No.46, Singarathope, Trichy-620008, Tamilnadu, India
Approved
HCG Multispeciality Ethics Committee, HCG Multi Speciality Hospital, Mithakhali, Ellisbridge,Ahmedabad-380006
Approved
HCG Vadodra Ethics Committee, HCG Cancer Centre, Sun Pharma Road, Opp Satsang Party Plot, Vadodra-390012.
Approved
Institute Ethics Committee,Shree Himalaya cancer Hospital and Research Institute, 4, vinod garden, Behind Sanman hotel, Jetalpur Bridge, Alkapuri, Vadodra-390007
Approved
Institutional Ethics Commiittee, Prince Aly Khan Hospital, Mazagaon, Mumbai 400010, India
Approved
Institutional Ethics Committee Apex Hospital Pvt. Ltd, Sp 4 & 6 MIA Malviya Nagar, near apex circle, Jaipur-302017
Approved
Institutional Ethics Committee Bhagwan Mahaveer Cancer Hospital & Research Centre Jawahar Lal Nehru Marg Malviya Nagar, Jaipur- 302017, Rajasthan India
Approved
Institutional Ethics Committee Deenanath Mangeshkar Hospital and Research Center, Erandawane, Pune 411004, India
Approved
Institutional Ethics Committee Erode Cancer Centre 1/393, Velavan Nagar, Perundurai Road, Thindal, ERODE, Tamil Nadu-638012 India
Approved
Institutional Ethics Committee HCG Curie City cancer Centre # 444-1-1/3, Padavalareu, Gundala, Vijayawada 520002, Andhra Pradesh, India.
Approved
Institutional Ethics Committee of Mysore Medical College & Research Institute and Associated Hospitals, Dept. Of Pathology, K.R. Hospital, Mysore – 570021
Approved
Institutional Ethics Committee Poona Medical Research Foundation, E 4-C to E 4-F, 4th Floor, Fifth Avenue Condominium, Dhole Patil Road, Pune – 411001
Approved
Institutional Ethics Committee R.G. Kar Medical college 2nd Floor, Platinum Jubilee Building, 1, Khudiram Bose Sarani, Kolkata-700004, West Bengal, India
Approved
Institutional Ethics Committee sparsh Hospital, Sparsh Hospital & critical care Private Ltd, Plot no-A/407, Saheednagar, Bhubaneswar-751007 Odisha, India,
Approved
Institutional Ethics Committee, KAHER (formerly known as KLE University). JNMC Campus, Nehru Nagar, Belgavi-590010
Approved
Institutional Ethics Committee-Clinical Studies Apollo Research Innovation(ARI) Sarita Vihar, Delhi-Mathura Road, New Delhi-110076
Approved
Institutional Ethics Committee-Clinical Studies Apollo Research Innovation(ARI) Sarita Vihar, Delhi-Mathura Road, New Delhi-110076
Approved
Institutional Review Board Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, New Delhi- 110085, India
Approved
MNJ Institute of Oncology and Regional Cancer Centre Ethics Committee, Red Hills, Hyderabad-500004, Telangana,
Sapathgiri Institute of Medical Sciences and Research Centre Institutional Ethics Committee #15, Chikkasandra, Hesaraghatta Main Road, Banglore-560090
Approved
SCCMH-Institutional Ethics Committee No.36, 1st Main Road, 5th Cross Nethravathi Street Maruthi Nagar, Nagarbhavi Main Road, Bangalore -560072, Karnataka, India
1.Female subjects of age 18 to 65 years (both inclusive).
2.Subject with pathologically (histologically or cytologically) confirmed, uni-dimensionally measurable invasive metastatic breast cancer.
3.Subjects with a strong HER-2 over-expression as described by a 3+ score by immunohistochemistry (IHC) or a positive fluorescence in-situ hybridization (FISH).
4.For the treatment of subjects with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Subject should have either:
• Received prior therapy for metastatic disease, or
• Developed disease recurrence during or within six months of
completing adjuvant therapy.
5.Subject with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
6.Left ventricular ejection fraction (LVEF) ≥50% by 2 D ECHO.
7.Subjects with following laboratory results:
• Absolute neutrophil count >1500 cells/mm3
• Platelet count >100,000 cells/mm3
• Hemoglobin ≥9.0 g/Dl
• Total bilirubin ≤1.5 upper limit of normal (ULN)
• AST, ALT and alkaline phosphatase ≤ 2.5 X ULN.
8.Subjects must have recovered from all treatment related toxicities prior to randomization.
9.Pregnancy-related inclusions, including:
•Subjects with negative serum pregnancy test at trial start
•Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and till the end of study visit. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
10.Ability to comply with study and follow – up procedures and provide written informed consent.
11.Patient with life expectancy of minimum of 7 months at screening.
ExclusionCriteria
Details
1.Subject with history of Trastuzumab emtansine treatment.
2.Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease).
3.History of symptomatic chronic heart failure (New York Heart Association [NYHA] Classes II-IV) or serious cardiac arrhythmia requiring treatment.
4.Current uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or unstable angina.
5.Pregnancy or lactation.
6.Current known active infection with HIV, hepatitis B virus, or hepatitis C virus.
7.Have a history of hypersensitivity to the Trastuzumab emtansine 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 subject unsuitable for participation in the study.
9.Any chemotherapy, hormonal therapy, radiotherapy or surgery for the treatment of breast cancer within 3 weeks of screening.
10.Have any concurrent disease or condition that, in the opinion of the investigator, would make the subject unsuitable for participation in the study.
11.Have any other medical or psychiatric condition that could compromise study participation.
12.Current clinical or radiographic evidence of Central nervous metastates.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To compare the overall response rate (ORR) following administration of ZRC-3256 (Cadila Healthcare Limited) and Kadcyla® in patients with metastatic breast cancer based on Response Evaluation Criteria in Solid Tumors (RECIST, Version 1.1) achieved at end of 24 weeks.
Timeframe: Week 0 (baseline), week 24 (visit 15)
Secondary Outcome
Outcome
TimePoints
1. To compare the pharmacokinetic parameters (Cmax, AUC0-t )
2. To compare the incidence and titres of Anti-Drug Antibodies at the end of 12 weeks (visit 11) and 24 weeks treatment (visit 15)
3. Comparative safety for treatment emergent adverse events by monitoring of significant clinical signs and symptoms and laboratory abnormalities
1)Cycle 1
2)Week 0 (baseline), week 12 and week 24 (visit 15)
3)Throughout the study.
Target Sample Size
Total Sample Size="168" Sample Size from India="168" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="168"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is Prospective,
Randomized, Multicenter, Comparative, Open-label, Parallel study to evaluate
the Efficacy, Safety and Pharmacokinetics of Test-Trastuzumab Emtansine (ZRC-3256;Cadila
Healthcare Ltd) and Reference-Trastuzumab Emtansine(Kadcyla®, Roche
Products (India) Pvt. Ltd.) in HER2- Positive Metastatic Breast Cancer Patients.