ADVANCED NON-SQUAMOUS NON-SMALL CELL LUNG CANCER - certain type of lungcancer
Conditions
Interventions
Day 1 of a 21-day cycle for each of at least 4 and no more than six (6) 21-day
cycles. Once paclitaxel and carboplatin have been stopped, treatment with
bevacizumab-Pfizer or
bevacizumab-EU is conti
Bevacizumab
NSCLC
Sponsors
Pfizer
Eligibility
Age
18 Years to 64 Years
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).;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. Screening scan (computed tomography [CT] or magnetic resonance imaging [MRI]) of the head, chest, abdomen (with adrenal glands), and other disease sites, as clinically indicated, to assess disease burden.;7. Eastern Cooperative Oncology Group (ECOG) Performance 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 or plasma creatinine *1.5 x upper limit of normal (ULN);;e. Urine dipstick proteinuria 1+ then a 24 hour urine for protein must have demonstrated urinary excretion of *500 mg of protein per day, or urine protein to creatinine ratio (UPC) ratio
Exclusion criteria
Exclusion criteria: 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 that is likely to bleed.;3. Known sensitizing EGFR mutations (for example, deletion 19 or L858R) or EML4-ALK translocation positive mutations.If mutation testing is performed, results must be reviewed and confirmed as negative for mutations prior to randomization.;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 NSCLC; prior neoadjuvant /adjuvant therapy is allowed if surgical resection for primary disease was performed.;6. History of local radiation for painful bone metastases in the last 2 weeks. (Patients with bone metastases are eligible, however those with symptomatic or painful bone metastases should not have received palliative local radiation for at least 2 weeks prior to randomization).;7. History of hemoptysis (>2.5 mL per event) in the last 3 months or severe bleeding. Evidence of current thrombotic or bleeding disorders. Therapeutic anticoagulation and/or coagulation abnormalities (eg, INR >1.5 and aPTT greater than ULN unless on prophylactic anticoagulation).;8. Medically uncontrolled hypertension or systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg.;9. Peripheral motor or sensory neuropathy with value of * grade 2.;10. Major surgery, or any investigational agents, within 4 weeks before the administration of the first dose of study treatment. Planned major surgery during the treatment period.;11. Any unhealed wound or bone fracture.;12. Active infection. Patients must be off anti-infective agents.;13. Comorbities that would increase the risk of toxicity.;14. Concurrent administration of other anticancer therapies. Bisphosphonate or Rank-Ligand inhibitor therapy for pre-existing bone metastases or osteoporosis is allowed.;15. Known central nervous system (CNS) metastases, as evidenced by appropriate scans, clinical symptoms, cerebral edema, and/or progressive growth (if a suspected CNS lesion is not confirmed by pathology).Treated and stable (asymptomatic; off steroids) brain metastases are allowed.;16. Active uncontrolled cardiac disease, such as cardiomyopathy, congestive heart failure (CHF) New York Heart Association (NYHA) functional classification of *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.;17. 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. Clinical contraindication to treatment with steroids preventing use as part of paclitaxel premedication.;19. Pregnant female patients; breastfeeding female patients; male patients with partners currently pregnant; patients able to father children and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study, and for at least 6
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, in accordance with Response Evaluations Criteria in Solid Tumors (RECIST) version 1.1. | — |
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 at 1 year from randomization; * Duration of response (DOR), 1 year progression-free survival (PFS) rate at 1-year survival rate from randomization; * Peak and trough bevacizumab-Pfizer and bevacizumab-EU concentrations at selected cycles up to 1 year from randomization; * Incidence of anti-drug (bevacizumab) antibodies (ADA), including neutralizing antibodies (NAb) up to 1 year from randomization; | — |
Countries
The Netherlands
Outcome results
None listed