A Clinical trial to evaluate the pharmacokinetics, safety, efficacy and immunogenicity of Bmab-100 and Avastin in patients with metastatic colorectal cancer
A Double Blind, Randomized, Active Controlled, Parallel Design, Comparative PK, Efficacy, Safety and Immunogenicity Study of Bmab-100 and Avastin®, both in Combination with XELOX Chemotherapy in Patients with Metastatic Colorectal Cancer
Apollo Speciality Hospital,
Department of Medical Oncology, Division-Clinical Research,
Padma Complex, No-320,
Anna Salai, Chennai-600035 Chennai TAMIL NADU
9940080233
srinivasangirija@gmail.com
Dr Patel Kaushalkumar Babubhai
Apple Hospital
Apple Hospital,
Udhna Darwaja,
Ring Road,Surat 39500 Surat GUJARAT
9723431102
drkaushalbpatel@gmail.com
Dr Jaiprakash Baraskar
Baraskar Hospital and Research Centre
Baraskar Hospital and Research Centre,Department- Medical Oncology,
276, Crystal Plaza, Central Bazar Road,
Ramdaspeth, Nagpur-440010 Nagpur MAHARASHTRA
9422108822
jpcancercare@gmail.com
Dr K R Madhava
BGS Global Hospitals
BGS Global Hospitals, Department of Cancer Institute,
BGS health & Education City, #67, Uttarahalli Road,
Kengeri, Bangalore- 560060, Karnataka. Bangalore KARNATAKA
9686724368
krmadhava1@gmail.com
DrPawan Kumar Agarwal
Bhagwan Mahaveer Cancer Hospital & Research Centre,
Bhagwan Mahaveer Cancer Hospital & Research Centre,
J.L.N. Marg, Malviya Nagar,
Jaipur - 302017, Rajasthan.
Nagpur 440025, Maharashtra
Jaipur RAJASTHAN
0141-2700107
sushilnagpur@yahoo.co.in
Dr Vishnu Aggarwal
BhaktiVedanta Hospital and Research Institute
BhaktiVedanta Hospital and Research Institute
Srishti Complex, Bhaktivedanta Swami Marg
Mira Road (East) Thane, MH, India 401107 Thane MAHARASHTRA
9969509226
drvmagarwal@gmail.com
Dr Satya Suresh Attili
BIBI General Hospital and Cancer Centre,
BIBI General Hospital and Cancer Centre,Department-Medical Oncology
16-3-991/1/C, Government Printing Press Road,
Malakpet, Hyderabad-500024 Hyderabad ANDHRA PRADESH
9246243034
sureshattili@yahoo.com
Dr Mammilapalli Gopichand
City Cancer Centre
City Cancer Centre,Department-Clinical Research, First floor, 33-25-33,
Ch.Venkata Krishnayya Street,
Suryarao pet, Vijayawada-520002 Hyderabad ANDHRA PRADESH
8662436661
mgopichand@yahoo.com
Dr Bhamare Sulabhchandra Atmaram
Curie Manavata Cancer Centre
Curie Manavata Cancer Centre, Department-Surgical Oncology OPD, Ground floor,
Opp Mahamarg Bus Stand, Mumbai Naka,
Nashik,422004 Nashik MAHARASHTRA
02532592666
ddrbhamare@mcrinasik.com
Dr Chetan Deshmukh
Deenanath Mangeshkar Hospital & Research Centre
Deenanath Mangeshkar Hospital & Research Centre,
Near Mathre Bridge, Erandawane,
Pune- 411004
Maharashtra, India Pune MAHARASHTRA
9850811449
drchetandeshmukh@gmail.com
Dr Surender Kumar Beniwal
Department of Medical Oncology, Acharya Tulsi Regional Cancer Institute & Research Centre,
"Department of Medical Oncology,
Acharya Tulsi Regional Cancer Institute & Research Centre,
S.P.Medical College & AG of Hospitals,
Bikaner-334003, Rajasthan,
"
Bikaner RAJASTHAN
9414370484
beniwal.surender@gmail.com
Dr Ashok Diwan
Government Medical College & Hospital,
Government Medical College & Hospital, Department of radiation therapy & oncology,
Nagpur - 440003 Nagpur MAHARASHTRA
9822816608
tinuad_07@hotmail.com
Dr Saurabh Satish Mohite
Grant Medical Foundation, Ruby Hall Clinic, New Cancer centre
Grant Medical Foundation, Ruby Hall Clinic,
New Cancer centre, 3rd Floor, No 40, Sassoon Road,
Pune-411001, India Pune MAHARASHTRA
9220451093
saurabhmohite1@gmail.com
Dr Shibashish Bhattacharya
Health Point Hospital,
Health Point Hospital,
#21, Prannath Pandit Street
(Opposite Lansdowne Padmapukur),
Kolkata-700025, West Bengal, India Kolkata WEST BENGAL
9051837235
shibashishbhattacharya@ymail.com
Dr Anjana Sainani
Jaslok Hospital and Research Center,
Jaslok Hospital and Research Center,
15, Dr. Deshmukh Marg, Pedder Road, Mumbai,
Maharashtra, 400026, IT Colony,
Cumballa Hill, Mumbai, Maharashtra 400026 Mumbai MAHARASHTRA
9820700132
anjanasainani@gmail.com
Dr Niraj Bhatt
Kailash Cancer Hospital & Research Centre
Kailash Cancer Hospital & Research Centre,Department-Clinical Research,
Muni Seva Ashram,
Po: Goraj, Ta: Waghodia,
Dist: Vadodara – 391760 Vadodara GUJARAT
King George’s Medical Institute, Lucknow, Uttar Pradesh,226003 Lucknow UTTAR PRADESH
9235042555
sameerdr79@gmail.com
Dr Anil Kumar N
M S Ramaiah Medical College and Hospitals
M S Ramaiah Medical College and Hospitals,
New BEL Road, MSRIT Post,
Bangalore-560054, Karnataka, India Bangalore KARNATAKA
9980446774
anianeel@gmail.com
Dr Kishore Singh
Maulana Azad Medical College, Lok Nayak Hospital,
Department of Radiotherapy,
Maulana Azad Medical College,
Lok Nayak Hospital,
New Delhi -110002 New Delhi DELHI
9810320341
docmadmax@gmail.com
Dr Randeep Singh
Max Super Speciality Hospital
Max Super Speciality Hospital,Department Clinical Research,
(A Unit of Balaji Medical and Diagnostic Research Centre)
108-A, Indraprastha Extension, Patpargaji,
Delhi-110092 New Delhi DELHI
9582449448
drrandeep.singh@maxhealthcare.com
Dr Pragnya Coca
Mazumdar Shaw Medical Centre, Narayana Hrudayalaya Private Limited,
Mazumdar Shaw Medical Centre, Narayana Hrudayalaya Private Limited,
NH Health City, No.258/A,
Bommasandra Industrial Area,
Hosur Road, Bangalore-560099,Karnataka, India Bangalore KARNATAKA
8050004989
pragnya.coca.dr@nhhospitals.org
Dr Sushil Mandhaniya
Meditrina Hospital
Meditrina Hospital
R-S 238, Central Bazar Road, Ramdaspeth,
Nagpur 440025, Maharashtra Nagpur MAHARASHTRA
9673063399
sushilnagpur@yahoo.co.in
Dr Vijaya Bhaskar Ramakrishnan
Meenakshi Mission Hospital & Research Centre
Meenakshi Mission Hospital & Research Centre,Department-Medical Oncology,Second Floor,
Lake Area, Melur Road,
Madurai-625107 Madurai TAMIL NADU
9443647481
drvijayabhaskar@yahoo.co.in
Dr Mukesh S
Mysore Medical College and Research Institute (K.R.Hospital)
Mysore Medical College and Research Institute (K.R.Hospital),
Irwan Raod, Mysore,
Karnataka-570001, India Mysore KARNATAKA
9886873788
dal_muk1@hotmail.com
Dr Ayyagiri Santa
ndo-American Cancer Hospital & Research Institute,
ndo-American Cancer Hospital & Research Institute,
Road # 14, Banjara Hills,
Hyderabad - 500 034 Hyderabad ANDHRA PRADESH
9848125174
santa_a2002@yahoo.com
Dr Rakesh Kapoor
Postgraduate Institute of Medical Education & Research,
Department of Radiotherapy, Nehru hospital
Sector 12, Postgraduate Institute of Medical Education & Research,
Chandigarh - 160 012 Chandigarh CHANDIGARH
9914209396
drkapoor.r@gmail.com
Dr Baijumon Balan
PVS Hospital (P) Ltd
PVS Hospital (P) Ltd,
Railway Station Road, Calicut-673002, Kerala. Kozhikode KERALA
9846552570
drbaijumonbalan@gmail.com
Dr C D Sivanandan
Regional Cancer Centre
Regional Cancer Centre
Post Box No.2417
Medical College Campus,
Thiruvananthapuram-695011,Kerala. Thiruvananthapuram KERALA
Shatabdi Hospital, Mumbai, Naka, Nashik, Maharashtra- 422001, India, Mumbai MAHARASHTRA
8888736446
drcvpethe@gmail.com
Dr Rudresha AH
Srinivasam Cancer Care Hospitals India Pvt. Ltd
Srinivasam Cancer Care Hospitals India Pvt. Ltd, #236/1, Vijayashree Layout, Arekere, Bannerghatta Main Road,Bangalore-560076, Karnataka, India Bangalore KARNATAKA
9480369521
rudresha.ah@gmail.com
Dr Prabagar
VGM Cancer care
VGM Cancer care ( A unit of VGM hospital)
No.2100, Trichy road,
Rajalakshmi mills stop,
Coimbatore-641005. Coimbatore TAMIL NADU
In patients with metastatic colorectal cancer (mCRC),
Intervention / Comparator Agent
Type
Name
Details
Intervention
Bmab-100
administered intravenously 7.5 mg/kg/body weight once every 3 weeks for 6 cycles.
Comparator Agent
Avastin (Roches bevacizumab)
to administer 7.5mg/kg once evry 3 weeks for 6 cycles
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Male and female patients aged 18 years and above
2. Histopathologically confirmed colorectal cancer.
3. Diagnosis of metastatic colorectal cancer which is not amenable to curative surgery and/or radiation
4. Part I of the study will include only patients who have received chemotherapy earlier for metastatic colorectal cancer [i.e. at least 1st line treatment failure mCRC patients]. Part II of the study will include only patients who have not received any treatment for metastatic colorectal cancer [i.e. only 1st line mCRC patients]
5. Measurable disease on radiological assessment according to RECIST 1.1 criteria
6. Patient is an eligible candidate for XELOX [capecitabine and oxaliplatin] chemotherapy and not suitable for surgery.
7. ECOG status 0 or 1 for part I of the study and ECOG status 0, 1 or 2 for part II of the study.
8. Have life expectancy of at least 4 months as per the investigator.
9. Women of childbearing potential and men must be using two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.) for the entire duration of the study from the time of screening and 4 months following the completion of therapy.
ExclusionCriteria
Details
1. Received prior chemotherapy for metastatic disease [chemotherapy for primary disease is acceptable] which is applicable for part II of the study only.
2. Prior treatment with bevacizumab
3. History of hemoptysis, thrombotic or hemorrhagic event in past 6 months
4. Therapeutic anticoagulation; regular use of aspirin (325 mg/day), NSAIDs or agents known to inhibit platelet function
5. Radiation therapy for metastatic disease or surgery within 1 month of randomization
6. Serious non-healing wound or bone fracture
7. Known hypersensitivity to bevacizumab, capecitabine or oxaliplatin
8. Uncontrolled hypertension [defined as either systolic blood pressure 150 mm of Hg or diastolic blood pressure 100 mm of Hg]
9. Urine protein on dipstick analysis ≥ 2+ [If urine protein is ≥2+, further assessments should show urine protein:creatinine ratio 0.5 grams protein per gram creatinine by urinalysis OR total urinary protein 1,000 mg by 24-hour urine collection for inclusion]
10. Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency.
11. High levels of SGOT 3 x ULN and 5 x ULN in patients with liver metastasis. Serum bilirubin 1.5 X ULN.
12. Hemoglobin 9 gm/dl or platelets 100,000/μl (with no blood and/ or packed cell transfusion within 2 weeks).
13. Patients with known or suspected brain metastases. Patients with a history of CNS metastases are eligible if they have been successfully treated and are off steroids for at least 4 weeks before randomization.
14. Patients with history of prior malignancy other than colorectal cancer.
15. Other invasive malignancy within the past 5 years except nonmelanoma skin cancer and successfully treated cervical carcinoma in situ.
16. Patients with severe renal impairment (estimated creatinine clearance below 30 mL/min)
17. Patients with clinically significant or poorly controlled co-morbid conditions like endocrinological, renal, hepatic, cardiac, pulmonary, hematological, gastrointestinal, neurological or psychological disorder, which in the opinion of the investigator may jeopardize the safety of the patient during the study or may interfere with the evaluation of efficacy of the study medication.
18. Patient in the opinion of investigator is not capable of complying with study requirements.
19. Patients with current history of drug/alcohol abuse.
20. Patient is unable or unwilling to give a written informed consent.
21. Patient has participated in an investigational drug study within last one month.
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
Single dose pharmacokinetic parameters for Bmab-100 and Avastin® in terms of AUC0-t and Cmax [Cycle 1]
Single dose pharmacokinetic parameters for Bmab-100 and Avastin® in terms of AUC0-t and Cmax [Cycle 1]
Secondary Outcome
Outcome
TimePoints
1.Overall response rate (ORR) according to RECIST 1.1 guidelines [baseline to 18 weeks]
2. Progression free survival (PFS) at 18 weeks
3. Multiple-dose pharmacokinetic parameters (Cmin) of Bmab-100 and Avastin® [Cycles 2 to 6]
4. Evaluation of comparative safety of Bmab-100 and Avastin® [over 18 weeks]
5. Evaluation of incidence and titres of ADA for Bmab-100 and Avastin® [over 18 weeks]
1. Overall response rate according to RECIST 1.1 criteria [baseline to 18 weeks]
2. Progression free survival (PFS) rate at 18 weeks
3. Multiple-dose pharmacokinetic parameters (Cmin) of Bmab-100 and Avastin® [Cycles 2 to 6]
4. Evaluation of comparative safety of Bmab-100 and Avastin® [over 18 weeks]
5. Evaluation of incidence and titres of ADA for Bmab-100 and Avastin® [over 18 weeks]
Target Sample Size
Total Sample Size="146" Sample Size from India="146" Final Enrollment numbers achieved (Total)= "146" Final Enrollment numbers achieved (India)="146"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This study is randomized, double blind, parallel group, multi-centre trial comparing the PK, safety efficacy and immunogenicity of Bmab100 with Avastin in combination with xelox chemotherapy in 146 patient for a duration of 18 weeks