Carboplatin, Pemetrexed Disodium, and Bevacizumab in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: bevacizumab; carboplatin; pemetrexed
Intervention description: 5 mg/kg administered intravenously over 90 minutes on day 1 of each cycle (cycle = 3 weeks); Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle (1 cycle = 3 weeks); Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle (1 cycle = 3 weeks)
Intervention MeSH terms: Bevacizumab; Carboplatin; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; adenocarcinoma of the lung; bronchoalveolar cell lung cancer; large cell lung cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as carboplatin and pemetrexed disodium, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by stopping
      them from dividing. Pemetrexed disodium may also stop the growth of tumor cells by blocking
      some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can
      block tumor growth in different ways. Some block the ability of tumor cells to grow and
      spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
      Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor.
      Giving carboplatin and pemetrexed disodium together with bevacizumab may kill more tumor
      cells.

      PURPOSE: This phase II trial is studying how well giving carboplatin and pemetrexed disodium
      together with bevacizumab works in treating patients with stage IIIB, stage IV, or recurrent
      non-small cell lung cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically* or cytologically* confirmed non-small cell lung cancer

               -  Any histology, except squamous cell carcinoma, allowed

                    -  Mixed tumors will be categorized by the predominant cell type unless small
                       cell elements are present, in which case the patient is ineligible

               -  No histology in close proximity to a major vessel or cavitation NOTE: *Histologic
                  or cytologic elements may be established on metastatic tumor aspirates or biopsy

          -  Meets 1 of the following stage criteria:

               -  Stage IIIB disease (with malignant pleural effusion)

               -  Stage IV disease

               -  Recurrent disease

          -  Measurable or non-measurable disease

          -  No known CNS metastases by CT scan or MRI

        PATIENT CHARACTERISTICS:

        Age

          -  18 and over

        Performance status

          -  ECOG 0-1

        Life expectancy

          -  Not specified

        Hematopoietic

          -  Absolute neutrophil count > 1,500/mm^3

          -  Platelet count > 100,000/mm^3

          -  No history of hemorrhagic disorders

        Hepatic

          -  Bilirubin < 1.5 mg/dL

          -  AST and ALT < 5 times upper limit of normal

          -  INR < 1.5

          -  PTT normal

        Renal

          -  Creatinine clearance ≥ 45 mL/min

          -  Urine protein:creatinine ≤ 1.0 by spot urinalysis

        Cardiovascular

          -  No myocardial infarction within the past 6 months

          -  No New York Heart Association class II-IV congestive heart failure

          -  No unstable angina pectoris

          -  No serious cardiac arrhythmia requiring medication

          -  No stroke within the past 6 months

          -  No peripheral vascular disease ≥ grade 2

          -  No uncontrolled hypertension (i.e., blood pressure ≥ 150/100 mm Hg)

               -  Patients with a history of hypertension allowed provided blood pressure is well
                  controlled on a stable regimen of anti-hypertensive therapy

          -  No history of thrombotic disorders

          -  No other clinically significant cardiovascular disease

        Pulmonary

          -  No history of gross hemoptysis, defined as bright red blood of a ½ teaspoon or more

        Other

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Must be willing and able to take daily oral folic acid, intermittent vitamin B_12
             injections, and corticosteroid premedication

          -  No ongoing or active infection

          -  No serious, non-healing wound, ulcer, or bone fracture

          -  No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
             the past 6 months

          -  No psychiatric illness or social situation that would preclude study compliance

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  More than 3 weeks since prior immunotherapy

        Chemotherapy

          -  No prior systemic chemotherapy

        Endocrine therapy

          -  More than 3 weeks since prior hormonal therapy

        Radiotherapy

          -  See Disease Characteristics

          -  More than 3 weeks since prior radiotherapy

        Surgery

          -  More than 4 weeks since prior major surgery

          -  More than 1 week since prior minor surgery, fine needle aspiration, or core biopsy

          -  No concurrent major surgery

        Other

          -  Recovered from all prior therapy

          -  More than 4 weeks since prior and no concurrent participation in another experimental
             drug study

          -  No aspirin or other nonsteroidal anti-inflammatory drug (NSAID) 2 days before and 2
             days after each pemetrexed disodium infusion (5 days before and 2 days after each
             pemetrexed disodium infusion for NSAIDs with a long half-life [e.g., naproxen,
             rofecoxib, or celecoxib])

          -  No concurrent therapeutic anticoagulation

               -  Concurrent prophylactic anticoagulation for venous access devices allowed
                  provided requirements for INR and PTT are met

          -  No concurrent administration of any of the following:

               -  Chronic daily treatment with aspirin (> 325 mg per day)

               -  NSAIDs known to inhibit platelet function, including any of the following:

                    -  Dipyridamole

                    -  Ticlopidine

                    -  Clopidogrel

                    -  Cilostazol