Bevacizumab or Pemetrexed Disodium Alone or In Combination After Induction Therapy in Treating Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
Intervention: Paclitaxel; Carboplatin; Bevacizumab; Pemetrexed Disodium Heptahydrate
Intervention description: Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Paclitaxel; Bevacizumab; Carboplatin; Pemetrexed
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1516.0
Sex: All
Minimum age: 18 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 paclitaxel and carboplatin, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. 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 non-small cell lung cancer by blocking blood flow to the tumor. Pemetrexed disodium
      may stop the growth of tumor cells by blocking some enzymes needed for cell growth. It is not
      yet known whether giving bevacizumab or pemetrexed disodium alone or in combination is more
      effective in treating non-squamous non-small cell lung cancer.

      PURPOSE: This randomized phase III trial is studying bevacizumab and pemetrexed disodium
      alone or in combination after induction therapy to see how well they work in treating
      patients with advanced non-squamous non-small cell lung cancer.
    

Eligibility criteria:

        Inclusion Criteria (Step 1 Induction Therapy):

          -  Cytologically or histologically confirmed non-small cell lung cancer (NSCLC)

          -  Predominant non-squamous histology (NSCLC not otherwise specified allowed). Mixed
             tumors are categorized by the predominant cell type.

          -  Stage IV disease including M1a or M1b stages or recurrent disease

          -  Stage IIIB (T4NX) disease with ipsilateral lung lobe allowed provided patients are not
             candidates for combined chemotherapy or radiotherapy

          -  At least 12 months since prior adjuvant chemotherapy

          -  At least 2 weeks since prior radiotherapy

          -  Prior carboplatin allowed provided it was given as part of adjuvant chemotherapy

          -  Patients with brain metastasis must have received local therapy to the brain and have
             no evidence of progression in the brain for at least 2 weeks from the time of
             completion of local therapy, prior to registration

          -  ECOG (Eastern Cooperative Oncology Group) performance status 0-1

          -  Leukocytes ≥ 3,000/mm^3

          -  Absolute neutrophil count ≥ 1,500/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Total bilirubin ≤ institutional upper limit of normal (ULN)

          -  AST and ALT ≤ 3 times ULN

          -  Creatinine ≤ institutional ULN OR creatinine clearance ≥ 60 mL/min

          -  Urine protein:urine dipstick ≤ 0-1+ (if > 1+, urine protein creatinine ratio must be <
             1)

          -  Measurable or non-measurable disease as defined by RECIST (Response Evaluation
             Criteria in Solid Tumours) criteria

          -  Patients with hypertension must be adequately controlled (BP < 150/100 mm Hg) with
             appropriate anti-hypertensive therapy or diet

          -  Concurrent therapeutic anti-coagulation allowed

          -  Fertile patients must agree to abstain from sexual intercourse or to use adequate
             contraceptive methods during and for at least 6 months after completion of study
             therapy

        Exclusion Criteria (Step 1 Induction Therapy):

          -  Prior malignancy within the past 3 years except superficial melanoma, basal cell
             carcinoma, or carcinoma in situ

          -  Prior systemic chemotherapy for advanced stage lung cancer

          -  Prior use of paclitaxel, pemetrexed disodium, or bevacizumab

          -  Major hemoptysis within the past 4 weeks

          -  Uncontrolled intercurrent illness including, but not limited to, active infection,
             symptomatic congestive heart failure, unstable angina pectoris, serious cardiac
             arrhythmia, psychiatric illness/social situations that would limit compliance with
             study requirements

          -  History of arterial thrombotic events or major bleeding within the past 12 months

          -  Major surgery such as thoracotomy, laparotomy, craniotomy, or significant traumatic
             injury within 6 weeks prior to registration. Biopsy procedures and chest tube
             insertion are not considered major surgery for the purpose of this protocol.

          -  Core biopsy within 7 days of registration

          -  Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
             recent peripheral arterial thrombosis) within the past 6 months

          -  Clinically significant cardiovascular disease

          -  Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the
             past 6 months

          -  History of serious non-healing wounds, ulcers, or bone fractures

          -  Cavitary lesions in the lungs

          -  Pregnant or nursing

          -  Concurrent anti-retroviral therapy in patients with HIV infection

        Inclusion Criteria (Step 2 Maintenance Therapy):

          -  Patient must have an overall stable or better response after 4 courses of induction
             therapy

          -  ECOG (Eastern Cooperative Oncology Group) performance status 0-1

          -  Patients must be registered to Step 2 within 6 weeks of the last day of chemotherapy
             administration on Step 1

          -  Acceptable bone marrow, renal and hepatic function within 2 weeks of registration