Health Condition 1: null- NSCLC â?? Non Small Cell Lung Cancer
Conditions
Interventions
Intervention1: 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
Sponsors
Pfizer Limited
Eligibility
Inclusion criteria
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 investigatorâ??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 e.Urine dipstick proteinuria 1+ then a 24 hour urine for protein must have demonstrated urinary excretion of Liver Function f.Total bilirubin g.Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) 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 laboratoryâ??s reference range for postmenopausal women.
Exclusion criteria
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. 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 patientâ??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 patientâ??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 investigatorâ??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 premed
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. Timepoint: Every 6 weeks (±7 days) until Week 25 (based on date of randomization). | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 antibodiesTimepoint: 1 Year | — |
Countries
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
Contacts
Public ContactDr Seema Pai
Pfizer Limited
Outcome results
None listed