Chemotherapy With or Without Bevacizumab in Treating Patients With Stage IB, Stage II, or Stage IIIA Non-small Cell Lung Cancer That Was Removed By Surgery
Condition: Stage IB Lung Non-Small Cell Carcinoma AJCC v7; Stage IIA Lung Non-Small Cell Carcinoma AJCC v7; Stage IIB Lung Non-Small Cell Carcinoma AJCC v7; Stage IIIA Lung Non-Small Cell Cancer AJCC v7
MeSH terms: Carcinoma; Carcinoma, Non-Small-Cell Lung
Intervention: Bevacizumab; Cisplatin; Docetaxel; Gemcitabine Hydrochloride; Laboratory Biomarker Analysis; Pemetrexed Disodium; Questionnaire Administration; Vinorelbine Tartrate
Intervention description: Given IV; Given IV; Given IV; Given IV; Correlative studies; Given IV; Ancillary studies; Given IV
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Cisplatin; Gemcitabine; Docetaxel; Pemetrexed; Vinorelbine; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1501.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies chemotherapy and bevacizumab to see how well they
      work compared to chemotherapy alone in treating patients with stage IB, stage II, or stage
      IIIA non-small cell lung cancer that was removed by surgery. Drugs used in chemotherapy work
      in different ways to stop the growth of tumor cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. Giving more than one drug
      (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as
      bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab
      also may stop the growth of non-small cell lung cancer by blocking the growth of new blood
      vessels necessary for tumor growth. It is not yet known whether chemotherapy is more
      effective with or without bevacizumab in treating non-small cell lung cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  In order to be eligible for this trial, patients must have undergone complete
             resection of their non-small cell lung cancer (NSCLC) [stage IB (>= 4 cm)] - [IIIA
             (T2-3N0, T1-3N1, T1-3N2] prior to enrollment; accepted types of resection will consist
             of lobectomy, sleeve lobectomy, bi-lobectomy or pneumonectomy; resections by
             segmentectomy or wedge resection will not be accepted; mediastinal lymph node sampling
             at specified levels is required pre-operatively (mediastinoscopy) or intraoperatively
             (level 7 and 4 for right sided tumors or level 7 and 5 and/or 6 for left sided tumors)

          -  Patients must be no less than 6 weeks (42 days) and no more than 12 weeks (84 days)
             post-thoracotomy at the time of randomization and must be adequately recovered from
             surgery

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Patients must not have received the following:

               -  Prior systemic chemotherapy at any time; methotrexate (MTX) given in low doses
                  for non-malignant conditions with last dose at least 2 weeks prior to date of
                  registration will be allowed; other low dose chemotherapeutics for non-malignant
                  conditions will be considered, but review by the study chair is required

               -  Hormonal cancer therapy or radiation therapy as prior cancer treatment within 5
                  years of randomization; (prior surgery, biologic therapy, hormonal therapy, or
                  radiation therapy for a malignancy over 5 years prior to enrollment that is now
                  considered cured is acceptable)

          -  Patients must not have any history of cancer within 5 years from randomization, with
             the exception of in-situ carcinoma of the cervix or completely resected non-melanoma
             skin cancer

          -  Absolute neutrophil count (ANC) >= 1500 mm^3

          -  Platelets >= 100,000/mm^3

          -  Prothrombin time/international normalized ratio (INR) =< 1.5

               -  Or, if patient is on therapeutic anticoagulation, prothrombin time/INR =< 3.0

          -  Partial thromboplastin time (PTT) =< institutional upper limit of normal (ULN) OR, if
             patient is on therapeutic anticoagulation, PTT must be =< 1.5 x ULN

          -  Total bilirubin =< 1.5 mg/dL

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) < 5
             x upper limit of normal (ULN)

          -  Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 5 x
             upper limit of normal (ULN)

          -  Serum creatinine =< 1.5 x institutional upper limit of normal (ULN)

          -  Urine protein should be screened by urine analysis for urine protein creatinine (UPC)
             ratio; for UPC ratio > 0.5, 24-hour urine protein must be obtained and the level must
             be < 1000 mg (1 g) for patient enrollment

          -  Patients with a known history of myocardial infarction or other evidence of arterial
             thrombotic disease (angina) will be allowed on study only if they have had no evidence
             of active disease for at least 12 months prior to randomization

          -  Patients with any history of cerebral vascular accident (CVA) or transient ischemic
             attack (TIA) will not be allowed on trial

          -  Women must not be pregnant or breast-feeding

               -  All females of childbearing potential must have a blood or urine test within 2
                  weeks prior to randomization to rule out pregnancy

          -  Both fertile men and women must agree to use adequate contraceptive measures during
             study treatment and for at least 6 months after completion of bevacizumab

          -  Patients must not have any clinically significant ongoing, active or serious
             infection, symptomatic or uncontrolled congestive heart failure, symptomatic or
             uncontrolled cardiac arrhythmia or any other medical condition or psychiatric
             illness/social situations that would limit compliance with study requirements

          -  Patients must have no history of bleeding diathesis or coagulopathy

          -  All patients must have a documented blood pressure (BP) with systolic =< 150 and
             diastolic =< 90 within 28 days of registration; patients with known hypertension must
             be on a stable regimen of anti-hypertensive therapy

          -  Patients receiving daily treatment with aspirin or non-steroidal anti-inflammatory
             agents (NSAIDS) are eligible; treatment with dipyridamole (Persantine), ticlopine
             (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal) is not allowed; patients
             must have stopped taking any of these agents at least 7 days prior to randomization

          -  Patients must not have serious non-healing wound, ulcer, bone fracture, or have
             undergone a major surgical procedure, open biopsy, or significant traumatic injury
             within 28 days prior to randomization OR core biopsy within 7 days prior to
             randomization

          -  Patients must not have a history of abdominal fistula, gastrointestinal perforation or
             intra-abdominal abscess within 28 days prior to randomization

          -  Patients must not have any anticipated major surgical procedure(s) during the course
             of the study

          -  Patients must not have known hypersensitivity to Chinese hamster ovary cell products
             or other recombinant human antibodies

          -  Patients may be on a stable regimen of therapeutic anticoagulation or may be receiving
             prophylactic anticoagulation of venous access devices, provided that coagulation
             studies meet entry criteria above; caution must be exercised for patients requiring
             anticoagulation, including treatment with low dose heparin or low molecular weight
             heparin for deep vein thrombosis (DVT) prophylaxis while on study

          -  Patients with ongoing post-operative hemoptysis (defined as bright red blood of 1/2
             teaspoon or more) are not eligible; patients with pre-operative hemoptysis that has
             resolved post-operatively are eligible

          -  Patients who will receive pemetrexed (pemetrexed disodium)/cisplatin therapy must also
             meet the following criteria:

               -  Patients assigned to pemetrexed/cisplatin therapy must NOT have squamous cell
                  histology

               -  Calculated creatinine clearance must be obtained within 2 weeks of randomization
                  and calculated creatinine clearance (CrCl) must be >= 45 mL/min using the
                  standard Cockcroft and Gault formula, or the measured glomerular filtration rate
                  (GFR) using the appropriate radiolabeled method ([51]chromium-labeled
                  ethylenediaminetetraacetic acid [51-CrEDTA] or technetium 99m
                  diethylenetriamine-pentaacetic acid [Tc99m-DTPA]) must be used to calculate CrCl