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CTRI Number  CTRI/2015/08/006109 [Registered on: 19/08/2015] Trial Registered Prospectively
Last Modified On: 06/06/2022
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, tolerability and efficacy of bevacizumab (Zydus Cadila) in nonsmall cell lung cancer (NSCLC) 
Scientific Title of Study   A Prospective, Randomized, Multi-Center Study to Compare the Safety, Tolerability and Efficacy of Bevacizumab (Zydus Cadila) With Bevacizumab (Avastin®) in Non-Small Cell Lung Cancer (NSCLC)  
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
BEV.14.001.02.PROT, version 2.0 , dated 29th April 2015  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)  
Name  Dr Deven Parmar  
Designation  Vice president  
Affiliation  Zydus Research Centre 
Address  Zydus Research Center, Survey No. 396/403, Sarkhej-Bavla National Highway No.8A Moraiya,

Ahmadabad
GUJARAT
382213
India 
Phone  91-2717-665555  
Fax  91-2717-665355  
Email  deven.parmar@zyduscadila.com  
 
Details of Contact Person
Scientific Query

Modification(s)  
Name  Dr Deven Parmar  
Designation  Vice president  
Affiliation  Zydus Research Centre 
Address  Zydus Research Center, Survey No. 396/403, Sarkhej-Bavla National Highway No.8A Moraiya, Ahmedabad 382213, India

Ahmadabad
GUJARAT
382213
India 
Phone  91-2717-665555  
Fax  91-2717-665355  
Email  deven.parmar@zyduscadila.com  
 
Details of Contact Person
Public Query

Modification(s)  
Name  Dr Deven Parmar  
Designation  Vice president  
Affiliation  Zydus Research Centre 
Address  Zydus Research Center, Survey No. 396/403, Sarkhej-Bavla National Highway No.8A Moraiya, Ahmedabad 382213, India

Ahmadabad
GUJARAT
382213
India 
Phone  91-2717-665555  
Fax  91-2717-665355  
Email  deven.parmar@zyduscadila.com  
 
Source of Monetary or Material Support  
Cadila Healthcare Limited  
 
Primary Sponsor  
Name  Cadila Healthcare Limited 
Address  Zydus Tower Satellite Cross Road, Ahmedabad 380015 Gujarat, 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 = 28  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Shankar Lal Jakhar  Acharya Tulsi Regional Cancer Treatment and Research Institute  Acharya Tulsi Regional Cancer Treatment & Research Institute, S.P. Medical College & AG Hospitals, Bikaner 334003,Rajasthan
Bikaner
RAJASTHAN 
9252385456

drsjakhar@rediffmail.com 
Dr Jayanti Patel   Apple Hospital  Apple Hospital,Udhna Darwaja,Ring Road,Surat-395002,Gujarat,India
Surat
GUJARAT 
9925852361

jayanthip@gmail.com 
Dr Mukul Goyal  Asian Cancer Research Institute  Asian Cancer Research Institute, Apex Hospital Private Limited, SP 4 and 6,Malviya Industrial Area, Malviya Nagar,Jaipur 302017
Jaipur
RAJASTHAN 
9530370043

drmukulgoyal@yahoo.in 
Dr Kaushal B Patel  BAPS Pramukhswami Hospital  BAPS Pramukhswami Hospital,Adajan Cross Road,Adajan,Surat-395009
Surat
GUJARAT 
9723431102

kaushalpatelbaps@gmail.com 
Dr Rahul Jiaswal  CIMS Hospital  CIMS Hospital, Near Shukan Mall, Off Science city Road,Sola,Ahmedabad-380060
Ahmadabad
GUJARAT 
8125632145

rahul.jaiswal@cimshospital.org 
Dr Abhishek Satyawan Jadhav  Curie Manavata Cancer Centre  Curie Manavata Cancer Centre, Opp. Mahamarg Bus Stand, Mumbai Naka,Nashik-422004,Maharshtra,India
Nashik
MAHARASHTRA 
9075525235

drabhishek@mcrinasik.com 
Dr Satya Pal Katarai   Department of Medical Oncology  Department of Medical Oncology,Vardhman Mahavir Medical College and Safdarjung hospital,New Delhi 110029
New Delhi
DELHI 
9868818541

spkataria@yahoo.com 
Dr Prabhat Singh Malik  Department of medical oncology AIMS  Department of medical oncology AIMS,Ansari nagar,New Delhi-110029
New Delhi
DELHI 
1168325318

drprabhatsm@gmail.com 
Dr Amit Dhiman  Department of Oncology  Department of Oncology,Dayanand Medical College & Hospital(DMCH),Ludhiana-141001
Ludhiana
PUNJAB 
9779898339

dramit.meet@gmail.com 
Dr Rajendra Kumar  Department of Radiology King Georges Medical University  Dept of Radiology King Georges Medical University, Shameena Road, Chowk, Lucknow Uttarpradesh-226003
Lucknow
UTTAR PRADESH 
9369918180

drrkumar10@gmail.com 
Dr Syamal kumar Sarkar   Department of Radiotherapy  Department of Radiotherapy,Medical College, 88, College street,Kolkata-700073
Kolkata
WEST BENGAL 
9831097315

drsarkarsmay@rediffmail.com 
Dr Bhavesh Parekh  HCG Cancer Centre  HCG Cancer Centre,Sola Science city road,Near Sola Bridge,S.G.highway,Ahmedabad-380060
Ahmadabad
GUJARAT 
9825034353

bhaveshdm1@hotmail.com 
Dr Shekar Patil  Healthcare Global Enterprises Limited  Healthcare Global Enterprises Limited, HCG Towers, No.8, P.Kalinga Rao Road, Sampangi Ram Nagar,Bangalore-560027
Bangalore
KARNATAKA 
9341245961

spassociates6@gmail.com 
Dr Narendra Khippal  Institute of Respiratory Diseases  Institute of Respiratory Diseases, SMS medical College and Attached Hospital, Subhash nagar shopping centre, shashtrinagar,Jaipur-302016
Jaipur
RAJASTHAN 
9829017619

dmkhippal@rediffmail.com 
Aloke Ghosh Dastidar   IPGME&R, SSKM  Department for Radiotherapy 244, AJC Bose Road Kolkata 700020
Kolkata
WEST BENGAL 
9831118494

alokeghoshdastidar@gmail.com 
Dr Siddharth Basu   IPGME&R, SSKM  Department for Radiotherapy 244, AJC Bose Road Kolkata 700020
Kolkata
WEST BENGAL 
9831135319

siddharthabasu24@gmail.com 
Dr Naveen Sharma  Malpani Multispeciality Hospital  SP-06, Road No. 1, VKI Area, Sikar Road, Jaipur 302013
Jaipur
RAJASTHAN 
9414248671

drbsharma@gmail.com 
Dr Sushil PMandhaniya   Mandhaniya cancer Hospital and Research Institute  Mandhaniya cancer Hospital and Research Institute, A-101, 1st floor, Neeti Gaurav Complex, 20 Central bazar Road, Adjacent to Hotel centre Point,Nagpur-440010
Nagpur
MAHARASHTRA 
9868315368

sushilnagpur001@yahoo.co.in 
Dr Sunil Kumar  Om Research Centre  Om Research Centre, Om Surgical Center and Maternity Home,SA-17/3, P-4, Sri Krishna Nagar, Paharia, Ghazipur Road, Varanasi-221007,Uttar Pradesh,India
Varanasi
UTTAR PRADESH 
8127413678

sun.1980pgi@gmail.com 
Dr Aniket Thoke  Sanjeevani CBCC Cancer Hospital  In front of Jain Mandir, Dawada colony,Pachpedi naka, Raipur, C.G. 492001
Raipur
CHHATTISGARH 
9752929741

drthoke@gmail.com 
Dr Dinesh Kumar Mangal  Soni Hospital  Soni Hospital, 38, Kanota Bagh, Jawahar lal Nehru marg, Jaipur-302004
Jaipur
RAJASTHAN 
9829011121

drdineshmangal@yahoo.co.in 
Dr K C Lakshmaiah   Sreenivasam Cancer Care Hospital  No 236-1,Vijayashree Layout , Arekere,Banerghatta, main Road,Banglore, 560072
Bangalore
KARNATAKA 
9448055949
08042099074
kcluck@gmail.com 
Dr Chiradoni Thungappa Satheesh  Sri Venkateshwara Hospital  Sri Venkateshwara Hospital, No. 86,Hosur Main Road,Madiwala,Bangalore-560068
Bangalore
KARNATAKA 
9242698750

svhospital1997@gmail.com 
Dr Neha Gupta  Sudbhawna Hospital  Sudbhawna Hospital, B31/80, 23 B- Bhogabir Lanka,Varanasi-221005
Varanasi
UTTAR PRADESH 
8004354185

drneha_500@yahoo.com 
Dr Sulabhachandra Atmaram Bhamare  Supe Heart and diabetes Hospital and Research Centre  Supe Heart and diabetes Hospital and Research Centre, Opp. Adharashram, Gharpure Ghat, Near Rungtha School, Ashok Stambh,Nasik-422002
Nashik
MAHARASHTRA 
9823061929

drsulabhchandra@yahoo.co.in 
Dr Asha S Aanand  The Gujarat Cancer and Research Institute  The Gujarat Cancer and Research Institute,NCH campus, Asarwa, Ahmadabad 380016
Ahmadabad
GUJARAT 
9924718992

gcriad1@bsnl.in 
Dr Shamsuddin Virani  Unique hospital Multispeciality and Research Institute  Unique hospital Multispeciality and Research Institute,Opp. Kiran Motor,Near Canal Civil Hospital Char rasta Sosyo circle lane,off ring Road,Surat-395002,Gujarat
Surat
GUJARAT 
9879855522

virani13@gmail.com 
Dr Prabagar Manickam  VGM Cancer Care  VGM Cancer Care (A unit of VGM Hospital), No. 2100, Trichy Road, Rajalakshmi mills stop,Coimbatore-641005
Coimbatore
TAMIL NADU 
9443681554

prabhagardr@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 28  
Name of Committee  Approval Status 
Apple Hospital Ethics Committee  Approved 
DTEC, DMC Ludhiana  Approved 
Ethics Committee All India Institute of Medical Sciences  Approved 
Ethics Committee BAPS Pramukh Swami Hospital  Approved 
Ethics Committee CIMS  Approved 
Ethics Committee Unique Hospital Multispeciality and Research Institute  Approved 
Ethics Committee, Sudbhawana Hospital  Approved 
Ethics Committee,S P Medical College and A G Hospitals  Approved 
Ethics committee-Shalby Limited, Ahmedabad  Approved 
GCRI/GCS Ethics Committee  Approved 
HCG Central Ethics Committee  Approved 
Institute Ethics Committee Sri Venkateshwara Hospital  Approved 
Institutional Ethics committee Apex Hospital Private Limited  Approved 
Institutional Ethics Committee for Human Research Medical College KolKata  Approved 
Institutional Ethics Committee Supe Hospital Supe heart and Diabetes Hospital and Research Centre  Approved 
Institutional Ethics Committee, VGM Hospital  Approved 
Institutional Ethics Committee, Malpani Multispeciality Hospital  Approved 
Institutional Ethics Committee, Om Surgical Center and Maternity Home   Approved 
Institutional Ethics Committee, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi  Approved 
IPGMER Research Oversight Committee  Approved 
IPGMER Research Oversight Committee  Approved 
Jasleen Hospitals Ethics Committee, Nagpur  Approved 
King Georges Medical University Institutional Ethics Committee  Approved 
Sanjeevani Cancer Hospital IEC,In front of Jain mandir, Dawada colony,Raipur, C.G. Indai  Approved 
Sanjeevani Cancer Hospital Institutional Ethics Committee,   Approved 
SEAROCK Ethics Committee SK Soni Hospital  Approved 
Srinivasam Cancer Care Hospital,Instituional Ethics Committee  Approved 
The Ethics Committee SMS Medical College and Attached Hospitals  Approved 
 
Regulatory Clearance Status from DCGI
Modification(s)  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C349||Malignant neoplasm of unspecifiedpart of bronchus or lung, non-squamous non-small cell lung cancer,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Bevacizumab (Reference Product, Avastin®)   Dosage:-Bevacizumab 15 mg/kg (IV infusion) plus paclitaxel 175 mg/m2 and carboplatin (AUC 5 mg/mL×min). Frequency:Day 01, Day 22, Day 43, Day 64, Day 85 and Day 106. route:-Intravenous 
Intervention  Bevacizumab (Test-Zydus)  Dosage:-Bevacizumab 15 mg/kg (IV infusion) plus paclitaxel 175 mg/m2 and carboplatin (AUC 5 mg/mL×min). Frequency:Day 01, Day 22, Day 43, Day 64, Day 85 and Day 106. route:-Intravenous  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  Patient of both sex aged ≥ 18 years
2. Patient with history of histologically or cytologically confirmed non-squamous non-small cell
lung cancer (defined as stage IIIB with malignant pleural effusion, stage IV, or recurrent
disease)
3. Patients with advanced, unresectable or metastatic non-squamous NSCLC suitable for
treatment with Bevacizumab, carboplatin and paclitaxel (BV and CP) therapy as a first line
therapy
4. Bidimensionally measurable lesion according to RECIST 1.1 criteria
5. Patients with Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2
6. Life expectancy of 12 weeks or more
7. Patients able to understand the investigational nature of this study and give written informed
consent prior to the participation in the trial
8. Able to comply with study requirement in opinion of Principal Investigator 
 
ExclusionCriteria 
Details  Pregnant and lactating women
2. Patient who have received prior chemotherapy or biotherapy, radiotherapy to an area
measurable disease (unless disease progression is documented following completion of the
therapy) or radiotherapy within past 2 weeks
3. History of clinically significant cardiac diseases (e.g., uncontrolled hypertension, myocardial
infraction, unstable angina, NYHA ≥2 congestive heart failure, or serious cardiac arrhythmia)
in past six months
4. History of serious or severe arterial thrombotic events and/or venous thromboembolic events
(cerebral infarction, myocardial infarction, stroke, active symptomatic peripheral vascular
disease; deep vein thrombosis, pulmonary embolism or proven coagulopathy in past three
months.
5. Recent or current use of aspirin or oral and/or parental anticoagulants (except low dose
Coumadin 1 mg), known hypersensitivity to any components of the study medications and
ingredients
6. History of surgery in past 4 weeks or planned elective surgery, fine needle biopsy, or an open
biopsy within past one week
7. Any other medical conditions (including mental illness, substance abuse, social situations)
deemed by the clinician
8. Patients with CNS metastasis
9. Gross hemoptysis (≥1/2 tsp red blood) or hematuria or hematemesis within 3 months
10. Absolute neutrophil count <1500/mm3
11. Platelets <100000/mm3
12. Creatinine level ≥1.5 mg/dL
13. Bilirubin level ≥1.5 × upper limit of normal (ULN)
14. Aspartate-aminotransferase(AST) and alanine-aminotransferase (ALT) levels ≥2.5 × ULN (≥5
× ULN for patients with liver metastases)
15. Alkaline phosphatase level ≥5 × ULN
Cadila Healthcare Limited
CLINICAL TRIAL PROTOCOL
BEV.14.001.02.PROT
CONFIDENTIAL
PAGE 7 OF 80
Prepared by:
Dr. Jayeshkumar Bhatt
Approved by:
Dr. R. H. Jani
Protocol No. BEV.14.001.02.PROT
Version No.: 2.0
16. Patient with non-healing wounds, ulcers or bone fractures
17. History of serious and / or severe infections such as Hepatitis C virus, hepatitis B virus, HIV
infections, tuberculosis, etc.
18. Simultaneous participation in other clinical trials, previous participation in other clinical trials
within 3 months before entering into the trial 
 
Method of Generating Random Sequence
Modification(s)  
Not Applicable 
Method of Concealment
Modification(s)  
Not Applicable 
Blinding/Masking
Modification(s)  
Open Label 
Primary Outcome  
Outcome  TimePoints 
Comparison of best overall response rate (ORR) following bevacizumab (Test Product, Zydus)
and bevacizumab (Reference Product) treatment in patients with non-squamous non-small cell
lung cancer 
Time Point :-Day 127 
 
Secondary Outcome  
Outcome  TimePoints 
Pharmacokinetics of bevacizumab following IV infusions of bevacizumab (Test Product, Zydus)
and bevacizumab (Reference Product, Roche/Genentech) till Day 22 after cycle 6 with
bevacizumab in patients with non-squamous non-small cell lung cancer (NSCLC) after single
dose.
To assess the safety, tolerability and immunogenicity of bevacizumab (Test Product, Zydus) and
bevacizumab (Reference Product 
Pharmacokinetics of bevacizumab following IV infusions of bevacizumab (Test Product, Zydus)
and bevacizumab (Reference Product, Roche/Genentech) till Day 22 after cycle 6 with
bevacizumab in patients with non-squamous non-small cell lung cancer (NSCLC) after single
dose. 
 
Target Sample Size   Total Sample Size="222"
Sample Size from India="222" 
Final Enrollment numbers achieved (Total)= "248"
Final Enrollment numbers achieved (India)="248" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   25/08/2015 
Date of Study Completion (India) 23/03/2017 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
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   NA 
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary
Modification(s)  

This is an A Prospective, Randomized, Multi-Center Study to Compare the Safety,Tolerability and Efficacy of Bevacizumab (Zydus Cadila) With Bevacizumab (Avastin®) in Non-Small Cell Lung Cancer (NSCLC) with Immunogenicity Assessment Extension study

The purpose of this study is to determine safety, tolerability, efficacy of bevacizumab (Test Product, Zydus) vs. bevacizumab (Reference Product, Roche/Genentech), in patients with unresectable, recurrent or metastatic non-squamous non-small cell lung cancer (NSCLC).

 
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