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CTRI Number  CTRI/2015/05/005757 [Registered on: 08/05/2015] Trial Registered Prospectively
Last Modified On: 03/09/2019
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Biological 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   A clinical trial to study the effects of Bevacizumab injection (Hetero) against Reference Medicinal Product (Reference product, Roche) in patients suffering from metastatic colorectal cancer 
Scientific Title of Study   A Prospective, Randomized, Multiple-Dose, Multi-Center, Comparative, Parallel Clinical Study to Evaluate the Efficacy, Safety, Immunogenicity and Pharmacokinetics of an Intravenous Infusion of Bevacizumab (Test product, Hetero) and Reference Medicinal Product (Reference product, Roche) Administered in Combination with Standard Chemotherapy in Patients of Metastatic Colorectal Cancer 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
HCR/III/BMAB/10/2013. Version No. 1.1, dated 02-Dec-2014  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query  
Name  Dr Shubhadeep Sinha MD 
Designation  Associate Vice-President and Head 
Affiliation  Hetero Drugs Ltd 
Address  Clinical Development and Medical Affairs, Hetero Drugs Limited, “Hetero Corporate”,7-2-A2, Industrial Estates, Sanath Nagar, Hyderabad- 500018, India

Hyderabad
ANDHRA PRADESH
500018
India 
Phone  91-40-23704923  
Fax  91-40-23801902  
Email  sd.sinha@heterodrugs.com  
 
Details of Contact Person
Public Query  
Name  Dr Rudolph Almeida 
Designation  Project Manager 
Affiliation  Hetero Drugs Ltd 
Address  Clinical Development and Medical Affairs, Hetero Drugs Limited, “Hetero Corporate”,7-2-A2, Industrial Estates, Sanath Nagar, Hyderabad- 500018, India

Hyderabad
ANDHRA PRADESH
500018
India 
Phone  91-40-23704923  
Fax  91-40-23801902  
Email  rudolph.a@heterodrugs.com  
 
Source of Monetary or Material Support  
Hetero Drugs Limited, Unit – III, Biologics Division, Survey no. 458, APIIC Pharma SEZ, Polepally (v), Jadcherla (m), Mahaboobnagar – 509301, A.P, India.  
 
Primary Sponsor  
Name  Hetero Drugs Limited 
Address  “Hetero Corporate”, 7-2-A2, Industrial Estates, Sanath Nagar, Hyderabad- 500018, India  
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 26  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Surendra Beniwal MD DM  Acharya Tulsi Regional Cancer Treatment & Research Institute  Acharya Tulsi Regional Cancer Treatment & Research Institute, S. P. Medical College & Ag of Hospitals, Bikaner-334003, Rajasthan
Bikaner
RAJASTHAN 		 01512226329

beniwal.surendra@gmail.com 
Dr Kirankumar PJadhav  B.J.Govt. Medical College & Sassoon General Hospital  B.J.Govt. Medical College & Sassoon General Hospital, Pune-411011, Maharashtra
Pune
MAHARASHTRA 		 0202612888

drkpjadhav@yahoo.co.in 
Dr Krishna Mohan DNB DM  Basavatarakam Indo American Cancer Hospital& Research Institute  Consultant Medical Oncologist, Department of Medical Oncology, Basavatarakam Indo American Cancer Hospital& Research Institute, Road No-14,Banjara hills,Hyderabad-500034
Hyderabad
ANDHRA PRADESH 		 040-23551235
040-235402120
mvtkm@yahoo.com 
Dr Vishnu Agarwal  Bhakti Vedanta Hospital  Bhakti Vedanta Hospital, shristi complex, Mera road, East dist., Thane-401017
Thane
MAHARASHTRA 		 02229452500

drvmagarwal@gmail.com 
Dr V Satya Suresh Attili MD DM  BIBI General Hospital and Cancer Center  BIBI General Hospital and Cancer Center 16-3-991/1/C, Government Printing Press Road, Malakpet, Hyderabad-500024
Hyderabad
ANDHRA PRADESH 		 040-24528134

Sureshattili@yahoo.com 
Dr Shailesh Patel  Bodyline hospital  Bodyline hospital, Opp Annapurna Hall, Nr. Dev status, New Vikas Gruh Road, Paldi, Ahmedabad-7,
Ahmadabad
GUJARAT 		 07926640505

dr.patelshailesh@yahoo.co.uk 
Dr Kalyan Kusum Mukherjee MD  Chittranjan national cancer institute  Incharge-Department of Medical Oncology, Chittranjan national cancer institute, 37 S.P Mukherjee road, Kolkata-700026.
Kolkata
WEST BENGAL 		 033-24759313
033-24757606
kkmukherjee4u@hotmail.com 
Dr Gopichand Mamillapalli MBBS MS DNB MCh  City Cancer Center  City Cancer Center, 33-25-33, Ch.Venkata Krishnaiah Street,Surya Rao Pet, Vijyawada-520002
Krishna
ANDHRA PRADESH 		 0866-2436661

mgopichand@yahoo.com 
Dr Amit Kumar Dhiman  Dayanand Medical College & Hospital  Dayanand Medical College & Hospital, Tagore Nagar, Civil Lines, Ludhiana-141001, Punjab
Ludhiana
PUNJAB 		 01614687700

dramit.meet@gmail.com 
Dr M Athar  GVSM Medical college  Dept. of surgery, GVSM Medical college, Kanpur - 208005
Kanpur Nagar
UTTAR PRADESH 		 07618800021

drathar.oncoresearch@gmail.com 
Dr Shekhar Patil MD DM  HCG Bangalore Institute of Oncology  HCG Bangalore Institute of Oncology, HCG Tower, #8, P.Kalinga Rao Road, Sampangiram Nagar, Bangalore-560027
Bangalore
KARNATAKA 		 080-40206000

spassociates6@gmail.com 
Dr Rajesh Kumar Singh  Indira Gandhi Institute of medical sciences  Indira Gandhi Institute of medical sciences, Sheikhpura, patna-800014
Patna
BIHAR 		 06122297361

drrajeshsingh@yahoo.com 
Dr Koushik Chatterjee  Institute of Post Graduate Medical Education and Research   Institute of Post Graduate Medical Education and Research ,244,AJC Bose road ,Kolkata -700024
Kolkata
WEST BENGAL 		 03322235181

drkoushik.chatterjee@gmail.com 
Dr Suresh H Advani MD FICP MNAMS  Jaslok Hospital & Research Centre  Jaslok Hospital& Research Centre, 15-Dr.G.Deshmukh Marg, Mumbai-400 026.
Mumbai
MAHARASHTRA 		 022-66573333
022-23520508
shadvani2000@yahoo.com 
Dr Sonia Tiwari  Jeevan Jyoti Multispecialty hospital   Jeevan Jyoti Multispecialty hospital & Infertility Research Centre, 162 Bai Ka Bagh, Lowther Road, Allahabad - 211003, Uttar Pradesh
Allahabad
UTTAR PRADESH 		 05322417248

tiwarisonia05@gmail.com 
Dr KSSethna   LTMMC & LTMGH  LTMMC & LTMGH, College building, 1st floor, Room No. 21, Sion, Mumbai-400022, Maharashtra
Mumbai
MAHARASHTRA 		 02224076381

kssethna@yahoo.co.uk 
Dr Murali Krishna Voonna  Mahatma Gandhi Cancer Hospital and Research Institut  Mahatma Gandhi Cancer Hospital and Research Institute, 1/7 MVP Colony, Vishakhapatnam-530017
Visakhapatnam
ANDHRA PRADESH 		 08912878787

muralivoonna@yahoo.com 
Dr Shibhashish Bhattacharya MD DM  Medical College Kolkata  Head Department of medical oncology Medical College Kolkata, College street, Kolkata-700073
Kolkata
WEST BENGAL 		 033-22123853
033-22123770
shibashishbhattacharya@ymail.com 
Dr Krishna Kumar Ratnam MD DM  Meenakshi Mission Hospital & Research Centre   Senior Consultant Medical Oncology Meenakshi Mission Hospital & Research Centre , Lake Area, Melur Road, Madurai-625107
Madurai
TAMIL NADU 		 0452-2588741

jalicecrc@yahoo.com 
Dr Sudha Sinha MD  MNJ Institute of Oncology & Regional Cancer Center  MNJ Institute of Oncology & Regional Cancer Center, Red Hills, Hyderabad-500004
Hyderabad
ANDHRA PRADESH 		 040-23318422

drsudhand35@gmail.com 
Dr Rakesh Kapoor  Post Graduate Institute of Medical education & Research   Post Graduate Institute of Medical education & Research ,Chandigarh - 160012
Chandigarh
CHANDIGARH 		 01722746018

drkapoor.r@gmail.com 
Dr Sandeep Jasuja MD DM  R.K.Birla Cancer Centre  Consultant Oncologist R.K.Birla Cancer Centre, SMS Medical College and Hospital, JLN Marg, Jaipur-302001
Jaipur
RAJASTHAN 		 0141-2560291

sandeepjasuja99@gmail.com 
Dr Sunil Kumar Guptha MD DM  Rajiv Gandhi Cancer institute & Research Centre  Sr. Consultant & Chief of Head & Neck Medical Oncology, Rajiv Gandhi Cancer institute & Research Centre (RGCI RC), Sector - V, Rohini, Delhi - 110 085, India,
New Delhi
DELHI 		 91-11-47022222

drsgonco@rediffmail.com 
Dr Ghanashyam Biswas MD DM  Sparsh Hospitals & Critical Care Pvt. Ltd  Sparsh Hospitals & Critical Care Pvt. Ltd. A/407, Shid Nagar, Bhubaneswar-751007, Orissa.
Khordha
ORISSA 		 0674-2540188

drgbiswas@yahoo.com 
Dr Girish Raju  St. John’s Medical College Hospital  St. John’s Medical College Hospital, Sarjapur Road, Bangalore-560034
Bangalore
KARNATAKA 		 08022065000

girisai_2004@yahoo.com 
Dr Satya Pal Kataria MD DM  Vardhman Mahaveer Medical College  Head Department of medical oncology Vardhman Mahaveer Medical College, Safdarjung Hospital, New Delhi-110029
New Delhi
DELHI 		 011-26165060

spkataria@yahoo.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 26  
Name of Committee  Approval Status 
Bodyline hospital ethics committee  Submittted/Under Review 
Central ethics committee, HCG  Approved 
Drug trial ethics committee-DMC  Submittted/Under Review 
Ethics committe-Mahatma Gandhi Cancer Hospital and Research Institute  Approved 
Ethics committee, BIBI General hospital & Cancer centre  Approved 
Ethics committee, MNJ institute of oncology & RCC  Submittted/Under Review 
Ethics committee, SMS Medical college  Submittted/Under Review 
Ethics committee, SP Medical college & AG Hospitals  Submittted/Under Review 
Ethics committee, Vardhman Mahavir medical college & Safdurjung Hospital  Approved 
Ethics committee-Bhakti Vedanta Hospital  Submittted/Under Review 
Ethics committee-BJMC-CTU  Submittted/Under Review 
Ethics committee-GSVM  Submittted/Under Review 
Ethics committee-IGIMS  Submittted/Under Review 
Ethics committee-PGI  Submittted/Under Review 
IEC-HR-LTMMC  Submittted/Under Review 
IEC-Jeevan Jyoti Hospital  Submittted/Under Review 
IEC-St. Johns Hospital  Submittted/Under Review 
Institutional Ethics committee, Basavatarakam Indo American Cancer Hospital & Research Institute  Approved 
Institutional Ethics committee, Chittranjan national cancer institute  Submittted/Under Review 
Institutional Ethics committee, City Cancer Centre  Approved 
Institutional Ethics committee, Jaslok Hospital& Research Centre  Approved 
Institutional Ethics committee, Medical college, Kolkata  Submittted/Under Review 
Institutional Ethics committee, Meenakshi Mission Hospital   Approved 
Institutional Ethics committee, Sparsh Hospital  Submittted/Under Review 
Institutional review board, Rajiv Gandhi Cancer institute & Research Centre (RGCI RC)  Approved 
IPGMER Research oversight committee  Submittted/Under Review 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C189||Malignant neoplasm of colon, unspecified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Bevacizumab (Hetero)  Bevacizumab is given at the dose of 7.5mg/kg, every 3 weeks for up to 08 cycles along with standard chemotherapy. Bevacizumab is given at the dose of 5mg/kg, every 2 weeks for up to 12 cycles along with standard chemotherapy.  
Comparator Agent  Bevacizumab (Roche)  Bevacizumab is given at the dose of 7.5mg/kg, every 3 weeks for up to 08 cycles along with standard chemotherapy. Bevacizumab is given at the dose of 5mg/kg, every 2 weeks for up to 12 cycles along with standard chemotherapy. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  1. Histologically pre-confirmed metastatic colorectal carcinoma, and not suitable for radical surgery, or radiotherapy at the inclusion time
2. No known brain metastases
3.Performance status - ECOG 0 to 2
4. Life expectancy ≥ 6 months
5. Major surgery, open surgical biopsy or significant traumatic injury at least 4 weeks before randomization. If post-operative, recovered from the effects of surgery
6. No plan to administer radiation therapy or perform surgery for target lesions during study treatment. (Palliative surgeries or radiation therapy for non-target lesions allowed).
7. INR ≤ 1.5 and aPTT ≤ 1.5 x ULN within 21 days prior to starting study treatment.
8. Adequate liver function: Serum bilirubin ≤ 1.5 x ULN; alkaline phosphatase and transaminases ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN)
9. Adequate bone-marrow function
10. Ability to comply with study and follow-up procedures and provide written informed consent
 
 
ExclusionCriteria 
Details  1. Drug allergy, hypersensitivity or intolerance: Known or suspected allergy or hypersensitivity to any component of Bevacizumab
2. Any anticancer treatment (chemotherapy, hormonal treatment, radiation treatment, surgery, immunotherapy, biologic therapy or tumor embolization) within 4 weeks before randomization3. Presence of a serious, non-healing wound, ulcer, or bone fracture
3. Chronic, actual or recent use (10 days prior to first drug administration) of acetylsalicylic acid (aspirin) >325 mg/day or clopidogrel (75 mg/day) or other treatments that can cause gastrointestinal ulcer (low-dose aspirin is permitted < or equal to 325 mg/day)
4. History of stroke or transient ischemic attack within 6 months prior to study enrolment
5. History or clinical evidence of uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg on repeated measurement) despite optimal medical management
6. Cardiac arrhythmia
7. Any medical, psychological, or social condition that may interfere with the subjects participation in the study or evaluation of the study results  
 
Method of Generating Random Sequence   Permuted block randomization, fixed 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Disease control rate as per RECIST 1.1 criteria  At baseline and end of treatment cycles 
 
Secondary Outcome  
Outcome  TimePoints 
Immunogenicity- Anti-Bevacizumab antibodies
Pharmacokinetic parameters (e.g., Cmax, Tmax & AUC etc.) Exploratory parameters- Estimation of VEGF levels
Quality of life: Comparison of Quality of Life (QoL) scores (FACT-C & Treatment Outcome Index)
Safety: Adverse events by monitoring of significant clinical signs, symptoms & laboratory abnormalities during treatment.
 		 Immunogenicity- Anti-Bevacizumab antibodies from baseline to end of treatment cycles
Pharmacokinetic parameters will be calculated at end of first treatment cycle Exploratory parameters- Estimation of VEGF levels from baseline to the end of treatment cycles
Quality of life: Comparison of Quality of Life (QoL) scores from baseline to EOT

 
 
Target Sample Size   Total Sample Size="111"
Sample Size from India="111" 
Final Enrollment numbers achieved (Total)= "137"
Final Enrollment numbers achieved (India)="137" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   12/05/2015 
Date of Study Completion (India) 16/03/2017 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) 16/03/2017 
Estimated Duration of Trial   Years="2"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details    
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary   This is an open label, randomized, multi-center, multiple-dose, parallel study to evaluate the safety and efficacy of intravenous infusion of Bevacizumab Test product (Hetero) and Reference product in treatment of metastatic colorectal cancer given along with standard chemotherapy regimen. The primary objective is to compare the DCR using RECIST 1.1 criteria between two formulations. The secondary objectives are to evaluate safety, compare the immunogenic potentials and estimation of VEGF from baseline to the end of chemotherapy cycles between two formulations of Bevacizumab (test and reference). Comparison of single dose pharmacokinetic characteristics at the end of first cycle of chemotherapy and quality of life in both the groups will be evaluated. 
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