A Comparative Study Of PF-06439535 Plus Paclitaxel-Carboplatin And Bevacizumab Plus Paclitaxel-Carboplatin Patients With Advanced Non-Squamous non small cell lung cancer.

Phase 3

Active, not recruiting

• Conditions: NSCLC – Non Small Cell Lung Cancer

• Registration Number: CTRI/2016/01/006522
• Lead Sponsor: Pfizer Limited

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.xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-02-22
• Last Update Posted: 2019-07-16

Recruitment & Eligibility

• Status: Closed to Recruitment of Participants
• Sex: All
• Target Recruitment: 798

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Measures

Name	Time	Method
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;

Trial Locations

Locations (10)

Bhagwan Mahaveer Cancer Hospital And Research Centre; 🇮🇳 Jaipur, RAJASTHAN, India

HealthCare Global Enterprises Limited; 🇮🇳 Bangalore, KARNATAKA, India

Institute of Respiratory Diseases, SMS Medical College & Hospital; 🇮🇳 Jaipur, RAJASTHAN, India

Mahatma Gandhi Cancer Hospital and Research Institute; 🇮🇳 Visakhapatnam, ANDHRA PRADESH, India

Noble Hospitals Pvt Ltd; 🇮🇳 Pune, MAHARASHTRA, India

Regional Cancer Centre; 🇮🇳 Thiruvananthapuram, KERALA, India

Sahyadri Speciality Hospital; 🇮🇳 Pune, MAHARASHTRA, India

Shalby Hospitals; 🇮🇳 Ahmadabad, GUJARAT, India

Shatabdi Super Speciality Hospital; 🇮🇳 Nashik, MAHARASHTRA, India

Tata Memorial Hospital; 🇮🇳 Mumbai, MAHARASHTRA, India

Bhagwan Mahaveer Cancer Hospital And Research Centre

🇮🇳Jaipur, RAJASTHAN, India

Dr Lalit Mohan Sharma

Principal investigator

09828683771

drlalit2003@yahoo.com