CTRI/2017/02/007805 [Registered on: 07/02/2017] Trial Registered Prospectively
Last Modified On:
04/04/2017
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
Lung cancer clinical study comparing efficacy, safety and immunogenicity of CBT124 (Bevacizumab Candidate Biosimilar) with EU-sourced Avastin®.
Scientific Title of Study
A Randomized, Double-blind, Multicentric,
Parallel-group Study Comparing Efficacy, Safety and
Immunogenicity of CBT124, a Candidate Biosimilar
Bevacizumab in Combination with Carboplatin and
Paclitaxel with EU-sourced Avastin® in Combination
with Carboplatin and Paclitaxel in First-line Treatment
for Subjects with Stage IV (Unresectable Recurrent
Disease or Metastatic) Non-squamous Non-Small Cell
Lung Cancer (NSCLC)
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CBT124/CT/002
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, Department of Radiation oncology, P.B.M. Hospital Campus, S.P. Medical College, Bikaner-334003, Rajasthan Bikaner RAJASTHAN
9782300231
neetisharma@rediffmail.com
Dr Siddhartha Nanda
All India Institute Of Medical Sciences
All India Institute Of Medical Sciences, Department of Radiation oncology, Raipur, Tatibandh, G E Road, Raipur-492099, Chhattisgarh Raipur CHHATTISGARH
9713711888
sidnanda@aiimsraipur.edu.in
Dr Lalit Kumar
All Indian Institute of Medical Sciences (AIIMS)
All Indian Institute of Medical Sciences (AIIMS), Department of Medical oncology, Ansari Nagar East, New Delhi-110029 New Delhi DELHI
9811446828
lalitaiims@yahoo.com
Dr Wesley M Jose
Amrita Enterprises and Pvt Ltd.
Amrita Enterprises and Pvt Ltd., Department of Medical oncology, Amrita Institute of Medical Sciences, Amrita Lane, AIMS Ponekkara PO, Cochin-682041, Kerala Ernakulam KERALA
9287596275
wesleymjose@aims.amrita.edu
Dr Hari Goyal
Artemis Hospital
Artemis Hospital, Department of Medical oncology, Sector 51, Wazirabad Village, Gurgaon-122001, Haryana Gurgaon HARYANA
9958715678 9868086500 harig@artemishospitals.com
Dr Kirankumar Puna Jadhav
B. J. Govt. Medical College and Sassoon General Hospital
B. J. Govt. Medical College and Sassoon General Hospital, Dept. of Surgery, Pune Station, Pune-411001, Maharashtra Pune MAHARASHTRA
9823949126
drkpjadhav@gmail.com
Dr M Vikranth
City Cancer Centre
City Cancer Centre, Department of Surgical oncology, 33-25-33, Ch, Venkata Krishnayya Street, Suryarao Pet, Vijaywada - 520002, Andhra Pradesh Krishna ANDHRA PRADESH
9885256059 9642611888 mgopichand@yahoo.com
Dr Rajnish Nagarkar
Curie Manavata Cancer Centre
Curie Manavata Cancer Centre, Department of Surgical oncology, Opp. Mahamarg, Bust Stand, Mumbai Naka, Nasik-422004, Maharashtra Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr Amit Kumar Dhiman
Dayanand Medical College & Hospital (DMCH),
Dayanand Medical College & Hospital (DMCH), Ludhiana-141001, Punjab, India Ludhiana PUNJAB
9872188664
psharmaned@yahoo.co.in
Dr Chetan D Deshmukh
Deenanath Mangeshkar Hospital & Research Center
Deenanath Mangeshkar Hospital & Research Center, Department of Medical oncology, Near Mhatre Bridge, Erandawne, Pune-411004, Maharashtra Pune MAHARASHTRA
9850811449
drchetandeshmukh@rediffmail.com
Dr Randeep Singh
HCG SMH Curie Cancer Centre
HCG SMH Curie Cancer Centre, Department of Medical oncology, 2, Institutional Area, Vikas Marg Extension, Near Metro Pillar No. 116, Karkardooma, New Delhi-110092 New Delhi DELHI
9582449448
drrandeep@yahoo.co.in
Dr Kakali Chaudhary
Health Point Multispecialty Hospital
Health Point Multispecialty Hospital, Department of Radiation oncology, 21, Prannath Pandit street (opp. Lansdowne padmapukur), Kolkata- 700025, West Bengal Kolkata WEST BENGAL
9883083052
mailkakalichoudhury@gmail.com
Dr Mahesh Pawar
KEM Hospital
KEM Hospital, Department of Surgical oncology, Banjo Koradji building, Day Care Centre, Rastapeth, Pune-411011, Maharashtra Pune MAHARASHTRA
9823133390
drmaheshoncosurg@gmail.com
Dr Mukesh S
Krishna Rajendra Hospital
Krishna Rajendra Hospital, Department of Radiation oncology, Irwin Rd, Mysuru-570001, Karnataka Mysore KARNATAKA
9886873788
dal_muk1@hotmail.com
Dr Krishna Prasad
Manipal Centre For Clinical Research
Manipal Centre For Clinical Research, Department of Medical oncology, KMC Hospital, Attavar, Mangalore-575001, Karnataka Mandya KARNATAKA
9880345666
drkrishnaprasad@gmail.com
Dr C D Sivanandan
Regional Cancer Center
Department of Radiation Oncology, Regional Cancer Center, P.O Box No 2417, Medical College Campus, Thiruvanthapuram-69011, Kerala, India Thiruvananthapuram KERALA
9447882149 04712552065 sivanandancd@hotmail.com
Dr Sandeep Jasuja
Sawai Man Singh Hospital
Sawai Man Singh Hospital, Department of Medical oncology, J.L.N. Marg, Near Narayan Singh Circle, Jaipur-302004, Rajasthan Jaipur RAJASTHAN
9660121475
sandeepjasuja@gmail.com
Dr K C Lakshmaiah
Srinivasam Cancer Care Hospitals India Pvt. Ltd.
Srinivasam Cancer Care Hospitals India Pvt. Ltd., Department of Medical oncology, No. 236/1, Vijayashree Layout, Arekere, Bannnerghatta Main Road, Banglore-560076, Karnataka Bangalore KARNATAKA
9448055949
kcluck@gmail.com
Dr Ganesha Dev Vashishta
St. John’s Medical College Hospital
St. John’s Medical College Hospital, Department of Medical oncology, Sarjapur Road, Bangalore-560034, Karnataka Bangalore KARNATAKA
9972599314
ganesha1705@gmail.com
Dr Tanveer Maksud
Unique Hospital Multispecialty & Research Institute
Unique Hospital Multispecialty & Research Institute, Department of Medical oncology, Opp. Kiran Motors, Canal Road, Civil Hospital Char Rasta - Sosyo Circle Lane, Off. Ring Road, Surat-395002, Gujarat Surat GUJARAT
9909918887
tanveermaksud@yahoo.com
Dr Chirag J Desai
Vedanta Institute Of Medical Sciences
Vedanta Institute Of Medical Sciences, Department of Medical oncology, 1st Floor, Stadium Commerce College Road, Navrangpura, Near Samved Hospital, Ahmedabad-380009, Gujarat Ahmadabad GUJARAT
All India Institute of Medical Sciences, Rom No. 102, 1st Floor Old O.T. block, Ansari Nagar, New Delhi - 110029, India
Submittted/Under Review
Artemis Health Sciences Institutional Ethics Committee, Artemis Hospitals, Sector 51, Gurgaon – 122001, Haryana- India
Submittted/Under Review
Drug Trial Ethics Committee, Dayanad Medical College & Hospital, Tagore Nagar, Clivil lines, Ludhiana – 141001, Punjab, India
Submittted/Under Review
Ethics Committee of Care Institute of Medical Sciences , Opp. Panchamrut Bunglows, Nr, Shukan mall, Off Science city road, Sola, Ahmedabad-380060, Gujarat, India
Submittted/Under Review
Ethics Committee of KEM Hospital Research Centre, TDH bldg, Sardar Moodliar road, Rasta Peth, Pune, Maharashtra
Submittted/Under Review
Ethics Committee of SMS Medical College & attached Hospitals, Office of Ethics committee, Allergy Clinic, Dhanwantri OPD block, SMS Hospital, JLN Marg Jaipur - 302004
Submittted/Under Review
Ethics Committee, S.P. Medical College & AG of Hospitals, HRMC Cardiovascular Sciences & Research , Bikaner 334001, Rajasthan
Submittted/Under Review
Ethics Committee, Unique Hospital Multispecialty & Research Institute, Opp. Kiran Motors, Near Canal, Civil Char Rasta - Sosyo Circle Lane, Surat-395002, Gujarat, India
Approved
HCG-SMH Ethics Committee, HCG-SMH curie Cancer center, No. 2, Institutional Area, Vikas Marg Extension, Karkardooma, Delhi
Submittted/Under Review
Health Point Ethics Committee, # 21, Prannath Pandit street (opposite Lansdowne padmapukur), Kolkata- 700025, West Bengal, India
Submittted/Under Review
Human Ethics Committee Regional Cancer Centre, P.O. Box No. 2417, Medical College Campus, Thiruvananthapuram – 69011, Kerala, India
Submittted/Under Review
Institute Ethics Committee, All India Instiute of Medical Sciences, Raipur Tatibandh, G E Road, Chhattisagarh-492099
Submittted/Under Review
Institutional Ethics Committee , Mysore Medical College and Research Institute and Associated Hospitals, Mysore-570021
Submittted/Under Review
Institutional Ethics Committee Amrita Amrita Institute of Medical Sciences and Research Centre , Ponekkara P O, Cochin-682041, Kerala, India
Submittted/Under Review
Institutional Ethics Committee Deenanath Mangeshkar Hospital & Research Center, Off Karve Road, Erandwane Pune-411004, Maharashtra , India
Submittted/Under Review
Institutional Ethics Committee of B.J. Government Medical College and Sassoon Govt Hospital Pune 411001, Sassoon Road
Submittted/Under Review
Institutional Ethics Committee, City Cancer Centre, 33-25-33, Ch Venkata krishnayya street, suryarao pet, Vijaywada -520002, Andhra Pradesh, India
Submittted/Under Review
Manavata Clinical Research Institute Ethics Committee, Opp Mahamarg Bus stand, Mumbai Naka, Nashik-422004, Maharashtra, India
Submittted/Under Review
Manipal University Ethics Committee 7th floor, KMC Hospital Attavar, Mangalore-575001
Submittted/Under Review
Srinivasam Cancer Care Hospitals, 236/1, Vijayashree Layout, Bannerghatta Road, Omkar Nagar, Arekere, Banglore-560072, Karnataka, India
Approved
St. John’s Medical College Hospital Institutional Ethics Committee, Bangalore-560034, Karnataka, India
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
non-squamous Non-Small-Cell Lung Cancer (nsNSCLC),
1. Adult subjects aged ≥ 18 to 75 years (≥ 18 to 65 years for India) with histologically or
cytologically confirmed advanced non-squamous NSCLC. Mixed tumors should be
categorized according to the predominant histology
2. Epidermal growth factor receptor (EGFR) negative (for example, deletion exon 19 or
exon 21 point mutation L858R) or wild type mutations
3. No Kirsten rat sarcoma viral oncogene homolog (KRAS) and anaplastic lymphoma
receptor tyrosine kinase (ALK) positive subjects
4. Stage IV (Unresectable recurrent disease or metastatic) NSCLC
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
6. Evaluable disease status or measurable tumor
7. Life expectancy > 6 months.
8. Adequate hepatic, renal, and bone marrow function (alanine aminotransferase [ALT] and
aspartate aminotransferase [AST] < 2.5 × upper limit of normal [ULN], or ALT and AST
< 5 × ULN, if liver function abnormalities are due to underlying malignancy; total
bilirubin ≤ 1.5 × ULN; serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance
≥ 60 mL/min; urine dipstick < 1+ [i.e., 0 or traces]; international normalized ratio (INR)
≤ 1.5, and partial thromboplastin time ≤ ULN; absolute neutrophil count ≥ 1500/mm3;
platelet count ≥ 105/mm3; hemoglobin ≥ 9 g/dL). Subjects with a 1+ or greater urine
dipstick reading should undergo further assessment as per the clinical judgement of the
Investigator, including 24 hours urine collection or a laboratory protein/creatinine index
in urine (with quantitative protein determination in a full sized sample even if not
necessarily a 24 hours collection), as needed. Urinary protein should be < 100 mg/24
hours or protein/creatinine index of less than 0.2 mg/mgCreatinine or 15 mg/mmol
Creatinine.
9. Subjects with pre-existing hypertension must be well controlled on a stable regimen of
antihypertensive therapy. Have systolic blood pressure ≤ 140 and ≥ 90 mmHg, diastolic
blood pressure ≤ 90 and ≥ 50 mmHg and heart rate ≥ 40 and ≤ 90 bpm at screening and
admission. For single measurements in the 141 to 160 mmHg range (systolic) or in the 91
to 100 mmHg range (diastolic), a single repetition after resting for a few minutes (e.g. 5
minutes) on a supine position on the same day is allowed and, in this case, the mean of
both measurements will guide eligibility. The mean of both the measurements should be
≤ 140 mmHg (systolic) and ≤ 90 mmHg (diastolic).
10. Ability to understand risks of participation in the study and willingness provide informed
consent.
ExclusionCriteria
Details
1. Small cell lung cancer (SCLC) or combination of SCLC and NSCLC. Squamous-cell
tumors and mixed adenosquamous carcinomas of predominantly squamous nature
2. Known sensitizing EGFR mutations (for example, deletion exon 19 or exon 21
point-mutation L858R) or EML4-ALK translocation-positive mutations. Subjects with
KRAS mutations
3. Prior therapy with monoclonal antibodies or small molecule inhibitors against VEGF or
VEGF receptors, including bevacizumab
4. Prior therapy with carboplatin or paclitaxel
5. Prior systemic therapy for metastatic disease. Prior systemic anticancer therapy or
radiotherapy for locally-advanced NSCLC if completed < 12 months prior to screening
6. Evidence of a tumor that compresses or invades major blood vessels or tumor cavitation
that in the opinion of the Investigator is likely to bleed
7. Symptomatic brain metastasis (head computed tomography [CT]/magnetic resonance
imaging [MRI] is required within 6 weeks of study randomization)
8. Previous malignancy other than NSCLC in the last 5 years except for basal cell cancer of
the skin or pre-invasive cancer of the cervix
9. Any unresolved toxicity > Common Toxicity Criteria Grade 1 (except alopecia) from
previous anticancer therapy (including radiotherapy)
10. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of
bleeding. Thrombotic or hemorrhagic event ≤ 6 months prior to screening
11. History of hemoptysis greater than ½ teaspoon of bright red (fresh) blood in the past
4 weeks
12. Subjects receiving long-term aspirin (> 325 mg/day), or other non-steroidal
anti-inflammatory agents, or other drugs known to inhibit platelet function, treatment
with dipyridamole, ticlopidine, or clopidogrel
13. Subjects receiving anticoagulants
14. Subjects who plan to undergo surgery during the study period
15. Subjects who have undergone a major surgery, or have had a significant traumatic injury
within 4 weeks prior to randomization
16. Subjects who have a significant non-healing wound, or bone fracture within 4 weeks
prior to randomization
17. Subjects with history of gastrointestinal perforation or fistula formation
18. Subjects with known hypersensitivity to any of the ingredients of the investigational
products, or mammalian cell-derived products
19. Female subjects who are pregnant, breast-feeding, planning to be pregnant during the
study, or women of child-bearing potential (any woman who is not surgically sterile i.e.,
bilateral tubal ligation, total hysterectomy or < 2 years post menopause) not using a
reliable method of double contraception (e.g. condom plus diaphragm, condom or
diaphragm plus spermicidal gel/foam, tubal ligation, or stable dose of hormonal
contraception) throughout the study period
20. Male subject with a partner of childbearing potential (as mentioned in exclusion criteria
19) who does not consent to the use of a reliable method of double contraception (as
mentioned in exclusion criteria 19)
21. Subjects with uncontrolled hypertension
22. Subjects with active infection assessed to be clinically significant by Investigator
23. Known history of, or positive test result for human immunodeficiency virus (HIV),
hepatitis C virus (test for hepatitis C virus antibody [HCVAb]) or hepatitis B virus (test
for Hepatitis B surface Antigen [HBsAg])
24. History of alcohol or substance abuse
25. Prior treatment with any investigational drug within the 30 days prior to screening, or
within 5 half-lives of the drug, whichever is longer
26. Inability to comply with study requirements
27. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the
subject unsuitable for enrollment.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
Objective Response Rate (ORR) per RECIST criteria version 1.1.Objective response rate is defined as the proportion of subjects whose best confirmed overall
response over Week 1 to Week 19 is either complete response (CR) or partial response (PR).
Confirmed best overall response (complete or partial response) may be claimed only if the
criteria for each are met after a repeat radiologic tumor assessment (using RECIST criteria
version 1.1) 6 weeks later.
Safety (Proportion of subjects with selected adverse events (AE) of gastrointestinal perforation, hypertension, proteinuria, and pulmonary hemorrhage)
19 weeks and EoS
Target Sample Size
Total Sample Size="200" Sample Size from India="160" 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 Enrollment (India)
20/02/2017
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
20/02/2017
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="1" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Yet Recruiting
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?