Bevacizumab or Pemetrexed Disodium Alone or In Combination After Induction Therapy in Treating Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

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