CTRI/2016/01/006522 [Registered on: 14/01/2016] Trial Registered Prospectively
Last Modified On:
16/07/2019
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A Comparative Study Of PF-06439535 Plus Paclitaxel-Carboplatin And Bevacizumab Plus Paclitaxel-Carboplatin Patients With Advanced Non-Squamous non small cell lung cancer.
Scientific Title of Study
A PHASE 3 RANDOMIZED, DOUBLE-BLIND STUDY OF PF 06439535 PLUS PACLITAXEL-CARBOPLATIN AND BEVACIZUMAB PLUS PACLITAXEL-CARBOPLATIN FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH ADVANCED NON-SQUAMOUS NON-SMALL CELL LUNG CANCER
Trial Acronym
N/A
Secondary IDs if Any
Secondary ID
Identifier
B7391003
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)
Name
Dr Seema Pai
Designation
Director-India Cluster
Affiliation
Pfizer Limited
Address
Pfizer Limited, The Capital, 1802-1901, Plot No. C 70, G Block,, Bandra Kurla Complex, Bandra East, Mumbai, MAHARASHTRA,400051
The Capital, 1802/1901, Plot No. C-70, G Block, Bandra Kurla Complex, Bandra (East), Mumbai 400051, Maharashtra, India
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Argentina Australia Brazil Bulgaria Chile Croatia Czech Republic France Germany Greece Hong Kong Hungary India Italy Japan Malaysia Netherlands Peru Philippines Poland Romania Russian Federation Slovakia South Africa Spain Taiwan Thailand Turkey Ukraine United States of America
Sites of Study
No of Sites = 10
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Lalit Mohan Sharma
Bhagwan Mahaveer Cancer Hospital And Research Centre
Room no.240, First Floor Dept of Medical Oncology, Bhagwan Mahaveer Cancer Hospital, Jawahar Lal Nehru Marg,Jaipur-302017,
Rajasthan, India
Jaipur RAJASTHAN
09828683771 01412709716 drlalit2003@yahoo.com
Dr Satheesh CT
HealthCare Global Enterprises Limited
Room no.511,Dept of Medical Oncology, HealthCare Global Enterprises Limited,HCG Tower, #8, P. Kalinga Rao Road, Sampangi Ram Nagar,
Bangalore – 560027,
Karnataka, India
Bangalore KARNATAKA
09686600714 08040206059 drsatheeshct@gmail.com
Dr Narendra Khippal
Institute of Respiratory Diseases, SMS Medical College & Hospital
Room no 2, Dept of Chest and Respiratory, Institute of Respiratory Diseases, SMS Medical College & Hospital
B-2, Subhash Nagar Shopping Center, Jaipur – 302 016
Rajasthan, India
Jaipur RAJASTHAN
09829017619 01414007619 drnkhippal@rediffmail.com
Dr Murali Krishna Voona
Mahatma Gandhi Cancer Hospital and Research Institute
Room no.104, Dept of surgical Oncology, Mahatma Gandhi Cancer Hospital and Research Institute(A Unit of Vizag Hospital and Cancer Research Centre Private Limited)1/7, M.V.P. Colony, Visakhapatnam-530 017,
Andhra Pradesh, India
Visakhapatnam ANDHRA PRADESH
09848191287 08912506103 muralivoonna@yahoo.com
Dr Sumit Dhairyasheel Shah
Noble Hospitals Pvt Ltd
OPD no.4, Oncology Dept, Noble Hospitals Pvt Ltd, 153, Magarpatta City Road
Pune - 411013, Maharashtra, India
Pune MAHARASHTRA
07767858161 02043285126 drsumitdshah@gmail.com
Dr Sajeed Abdul Rahuman
Regional Cancer Centre
Room no 8326, Dept of Radiation Oncology, Regional Cancer Centre, Medical College Campus,
P.O. Box No-2417, Thiruvananthapuram-695011,
Kerala, India
Thiruvananthapuram KERALA
09447041690 04712552065 drsajeed.rcc@gmail.com
Dr Tushar Vishvasrao Patil
Sahyadri Speciality Hospital
Room no.114, Dept of Oncology, Sahyadri Speciality Hospital, 30C, Erandwane, Karve Road, Pune – 411004,
Maharashtra, India
Pune MAHARASHTRA
09552522556 02025459117 tussipats@hotmail.com
Dr Kajal M Shah
Shalby Hospitals
Room no.108,Dept of Oncology, Shalby Hospitals,Opp Karnavati Club, S.G. Highway, Ahmedabad – 380015, Gujarat, India
Ahmadabad GUJARAT
09714833369 07940203115 kajal.shah@shalby.org
Dr Vinayak Jibhau Shenage
Shatabdi Super Speciality Hospital
Room No.4,Surgical Oncology Dept, Shatabdi Super Speciality Hospital,Suyojit City Centre,Opp Mahamarg Bustand, Mumbai Naka,
Nashik – 422005,
Maharashtra, India
Nashik MAHARASHTRA
Room No. 225 Second floor, Oncology Dept (Thoracic), Tata Memorial Hospital,Dr Ernest Borges road, Parel
Mumbai - 400012
Maharashtra, India Mumbai MAHARASHTRA
09769331525 02224171734 dramitjoshi74@gmail.com
Details of Ethics Committee
No of Ethics Committees= 10
Name of Committee
Approval Status
Ethics Committee Mahatma Gandhi Cancer Hospital and Research Institute Institutional Review Board
Approved
Ethics Committee- Krishna Shalby Hospital
Approved
HCG- Central Ethics Committee
Approved
Human Ethics Committee Regional Cancer Centre
Submittted/Under Review
Institutional Ethics Committee – 1,Tata memorial Hospital
Submittted/Under Review
Institutional Ethics Committee Bhagwan Mahaveer Cancer Hospital and Research Centre
Approved
Noble Hospital Institutional Ethics Committee
Approved
Sahyadri Hospitals Ltd.Ethics Committee
Approved
Shatabdi Hospital Ethics Committee
Approved
The Ethics Committee, S.M.S Medical College and attached hospital
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
NSCLC – Non Small Cell Lung Cancer,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Bevacizumab-EU(AVASTIN)
Patients will be randomized to receive either bevacizumab-Pfizer or bevacizumab-EU in a 1:1 ratio. Dosing will be determined based on the body weight of the patient at the beginning of each 21-day cycle.
Bevacizumab-Pfizer and bevacizumab-EU will be administered once at the start of every 21-day cycle. The initial dose is 15 mg/kg delivered over 90 minutes as an intravenous infusion. If the first infusion is well tolerated, the second infusion may be administered over 60 minutes. If the 60-minute infusion is well tolerated, all subsequent infusions may be
administered over 30 minutes. If during the shortened infusions, infusion related reactions occur, the length of the infusion can be lengthened at the discretion of the clinician.
Bevacizumab-Pfizer or bevacizumab-EU will continue to be administered on Day 1 of every 3-week cycle after the chemotherapy has been discontinued. Bevacizumab-Pfizer or bevacizumab-EU will be administered until RECIST 1.1 defined disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, or withdrawal of consent occurs. No dose reduction is planned for bevacizumab-Pfizer or bevacizumab-EU.
Intervention
Bevacizumab-Pfizer(PF-06439535)
Patients will be randomized to receive either bevacizumab-Pfizer or bevacizumab-EU in a 1:1 ratio. Dosing will be determined based on the body weight of the patient at the beginning of each 21-day cycle.
Bevacizumab-Pfizer and bevacizumab-EU will be administered once at the start of every 21-day cycle. The initial dose is 15 mg/kg delivered over 90 minutes as an intravenous infusion. If the first infusion is well tolerated, the second infusion may be administered over 60 minutes. If the 60-minute infusion is well tolerated, all subsequent infusions may be
administered over 30 minutes. If during the shortened infusions, infusion related reactions occur, the length of the infusion can be lengthened at the discretion of the clinician.
Bevacizumab-Pfizer or bevacizumab-EU will continue to be administered on Day 1 of every 3-week cycle after the chemotherapy has been discontinued. Bevacizumab-Pfizer or bevacizumab-EU will be administered until RECIST 1.1 defined disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, or withdrawal of consent occurs. No dose reduction is planned for bevacizumab-Pfizer orbevacizumab-EU.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1.Male and female patients age ≥18 years of age, or ≥ age of consent in the region.
2.Newly diagnosed Stage IIIB or IV non-small cell lung cancer (according to Revised International System for Staging Lung Cancer criteria of 2010) or recurrent non-small cell lung cancer (NSCLC) for which they had not received chemotherapy for metastatic disease.
3.Histologically or cytologically confirmed diagnosis of predominately non-squamous NSCLC.
4.At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
5.For patients with recurrent disease, at least 6 months must have elapsed since completing adjuvant or neoadjuvant treatment.
6.Patients must have had a baseline scan (computed tomography [CT] or magnetic resonance imaging [MRI]) of the chest, abdomen, and other disease sites, as clinically indicated, to assess disease burden performed within 28 days prior to randomization.
7.Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
8.Screening laboratory values within the following limits (where deviation of up to 10% is acceptable for any single value if in the investigator’s opinion the patient does not have an increased safety risk):
Bone Marrow Function
a.Absolute neutrophil count (ANC) ≥1.5 x 109 cells/L (1500/mm3);
b.Platelet count ≥100 x 109 cells/L (100,000/mm3);
c.Hemoglobin ≥9.0 g/dL (90 g/L);
Renal Function
d.Serum creatinine ≤1.5 x upper limit of normal (ULN);
e.Urine dipstick proteinuria <2+ (ie, either 0, trace, or 1+). If urine dipstick is >1+ then a 24 hour urine for protein must have demonstrated urinary excretion of ≤500 mg of protein per day;
Liver Function
f.Total bilirubin ≤1.5 x ULN (<3 ULN if Gilbert’s disease);
g.Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 3 x ULN (≤ 5 x ULN if liver metastases are present).
9.Recovery (to Grade 1 or baseline) from all clinically significant adverse effects of prior therapies (excluding alopecia).
10.Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
11.Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
12.Male and female subjects of childbearing potential and at risk for pregnancy must agree to use two highly effective methods of contraception throughout the study and for at least 6 months after the last dose of assigned treatment (bevacizumab-Pfizer or bevacizumab-EU).
Female subjects who are not of childbearing potential (ie, meet at least 1 of the following criteria):
•Have undergone a documented hysterectomy and/or bilateral oophorectomy;
•Have medically confirmed ovarian failure; or
•Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level within the laboratory’s reference range for postmenopausal women.
ExclusionCriteria
Details
Exclusion Criteria:
Patients presenting with any of the following will not be included in the study:
1. Small cell lung cancer (SCLC) or combination SCLC and NSCLC. Squamous-cell tumors and mixed adenosquamous carcinomas of predominantly squamous nature.
2. Evidence of a tumor that compresses or invades major blood vessels or tumor cavitation.
3. Known sensitizing EGFR mutations (for example, deletion 19 or L858R) or EML4-ALK translocation positive mutations.
4. History of other cancer within 5 years prior to screening for this study, with the exception of adequately treated ductal carcinoma in situ of the breast, cervical carcinoma in situ, or basal or squamous cell skin cancer.
5. Prior systemic therapy for metastatic disease.
6. History of hemoptysis (more than 2.5 mL per event) in the last 3 months or severe bleeding. Evidence of current thrombotic or bleeding disorders. Systemic anticoagulation or chronic therapy with prescription non-steroidal anti-inflammatory drugs (NSAIDs), aspirin more than 325 mg, or other non-selective NSAIDs above the maximum allowed over the counter (OTC) dose, and/or coagulation abnormalities (eg, INR more than 1.5 and aPTT greater than ULN within 1 week prior to randomization). [Some NSAIDs have effects on platelet function (see Prescribing Information for the specific NSAID). In the event that a patient’s NSAID therapy exceeds the maximum dose of OTC medication, the investigator should contact the Sponsor for approval of patient inclusion. Approval will be based on the type of NSAID therapy, the dose, and the patient’s other known risk factors.]
7. Medically uncontrolled hypertension or systolic blood pressure more than 150 mmHg or diastolic blood pressure more than 100 mmHg.
8. Peripheral motor or sensory neuropathy with value of more than or equal to 2.
9. Major surgery, radiotherapy, or any investigational agents, within 4 weeks before the administration of the first dose of study treatment. Planned major surgery during the treatment period.
10. Any unhealed wound or bone fracture.
11. Infection requiring a course of systemic anti-infective agents within 3 weeks prior to randomization. Patients must be off of antibiotics for 7 days.
12. Comorbidities that would increase the risk of toxicity as per the investigator’s discretion.
13. Concurrent administration of other anticancer therapies. Bisphosphonate or Rank-Ligand inhibitor therapy for pre-existing bone metastases or osteoporosis is allowed.
14. Known central nervous system (CNS) metastases, as evidenced by appropriate scans, clinical symptoms, cerebral edema, and/or progressive growth.
15. Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (CHF) New York Heart Association (NYHA) functional classification of more than or equal to 3, unstable angina, or myocardial infarction within 12 months before first dose of study treatment. Clinically significant cardiovascular disease, peripheral vascular disease, transient ischemic attack, cerebrovascular accident.
16. History of severe hypersensitivity reaction to any of the products to be administered during the study, including mammalian cell derived drug products, taxanes, bevacizumab, murine proteins, or excipients in their formulations.
17. Clinical contraindication to treatment with steroids preventing use as part of paclitaxel premedication.
18. Pregnant female patients; breastfeeding female patients; male patients with partners currently pregnant; male and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol from at least 19 days prior to the first dose of study medication, for the duration of the study, and for at least 6 months after the last dose of investigational product (bevacizumab-Pfizer or bevacizumab-EU).
Note: For female patients of childbearing potential, to exclude the possibility of pregnancy, a serum or urine pregnancy test with sensitivity of at least 25 mIU/mL will be performed by the local certified laboratory, and 2 negative tests are required before receiving the first dose of investigational product. The second negative test should be at least 19 days after the first, and should be done during the first 5 days of the menstrual period, immediately preceding the first dose of the investigational product. In the absence of regular menstrual bleeding, the patient should have used 2 different methods of contraception for at least 1 month before the second pregnancy test. A patient is of childbearing potential if, in the opinion of the investigator, she is biologically capable of having children and is sexually active. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives.
19. Immunocompromised patients, including known seropositivity for human immunodeficiency virus (HIV).
20. Known or demonstrated hepatitis infection as listed below. Testing to demonstrate eligibility is required only in countries where regulations mandate testing. In all other countries, testing should be considered if a patient is at risk for having undiagnosed infection (for example due to history of injection drug use or due to geographic location).
a. Hepatitis B infection as detected by positive testing for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis B surface antibody (HBsAb).
b. Hepatitis C infection as detected by positive hepatitis C antibody (HCAb).
21. Participation in other clinical studies involving investigational drug(s) within 4 weeks before randomization and/or during study participation. Patients participating in observational studies not involving investigational drug(s) and/or long-term follow up of studies involving investigational drug(s) in which treatment was completed more than or equal to 4 weeks before randomization are not excluded.
22. Other severe acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
23. Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees directly involved in the conduct of the trial.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Objective Response Rate (ORR), evaluating the best response achieved by Week 19 and subsequently confirmed by 6 weeks thereafter, inaccordance with Response Evaluations Criteria in Solid Tumors (RECIST) version 1.1.
Every 6 weeks (±7 days) until Week 25 (based on date of randomization).
Secondary Outcome
Outcome
TimePoints
Safety characterized by type, incidence, severity, timing, seriousness,
and relationship to study therapy of adverse events, including cardiotoxicity and infusion-related reactions, and laboratory abnormalities;
Duration of response,1 year progression-free survival
rate and 1-year survival rate
Peak and trough bevacizumab-Pfizer and bevacizumab-EU
concentrations at selected cycles
Incidence of anti-drug (bevacizumab) antibodies, including neutralizing antibodies
1 Year
Target Sample Size
Total Sample Size="798" Sample Size from India="80" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is a multinational, double-blind, randomized, parallel-group Phase 3 clinical trial evaluating the efficacy and safety of bevacizumab-Pfizer plus paclitaxel and carboplatin and bevacizumab-EU plus paclitaxel and carboplatin by comparing the best confirmed objective response rate (ORR) by Week 19 in first-line treatment for patients with advanced (unresectable, locally advanced, recurrent or metastatic) non-squamous NSCLC.
Approximately 399 patients will be enrolled in each treatment arm for a total of approximately 798 patients at over 300 centers. Patients will be randomized (1:1) to receive either treatment of bevacizumab-Pfizer plus paclitaxel and carboplatin or bevacizumab-EU plus paclitaxel and carboplatin
Patients will participate in the study on average for approximately 13 months. This includes about 1 month of screening and at least 1 year for treatment and follow-up. Actual length of participation for individual patients will depend upon the actual duration of treatment. Minimum expected participation is 1 year unless shorter due to death, withdrawal of consent, or early termination of the trial.