Enzastaurin, Carboplatin, and Gemcitabine With or Without Bevacizumab in Treating Patients With Recurrent, Stage IIIB, or Stage IV Non-Small Cell Lung Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
• Stage IIIB (with confirmed malignant pleural effusion), stage IV, or recurrent disease
• Mixed tumors categorized by the predominant cell type are allowed provided no small cell elements exist
• Cytologic or histologic elements can be established on metastatic tumor aspirates or biopsy
• Measurable disease as defined by RECIST criteria
• No squamous cell carcinoma (group 1)
• No history of brain metastases (group 1)
• History of treated brain metastases allowed provided patient is not taking steroids and anti-seizure mediation (group 2)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 mg/dL
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 3 times ULN (≤ 5 times ULN with liver metastases)
• AST and ALT ≤ 3 times ULN (≤ 5 times ULN with liver metastases)
• INR < 1.5 or PTT normal (group 1)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during (groups 1 and 2) and for 6 months after completion of study treatment (group 1)
• No preexisting peripheral neuropathy ≥ grade 2
• Must be able to swallow tablets
• No cardiovascular condition, including any of the following:
• Myocardial infarction within the past 6 months
• Cerebrovascular ischemia or stroke within the past 6 months
• NYHA congestive heart failure > class II
• Unstable angina pectoris
• Serious cardiac arrhythmia requiring medication
• Significant vascular disease
• Symptomatic peripheral vascular disease
• No concurrent medical condition, psychiatric illness, or limitations that would limit study compliance
• No ongoing active infection or ongoing fever within the past 6 months
• No history of uncontrolled hypertension, defined as blood pressure ≥ 150/90 mm Hg despite being on a stable regimen of anti-hypertensive therapy
• No serious nonhealing wound, ulcer, or bone fracture within the past 4 weeks
• No ongoing or active infection
• No history of thrombotic or hemorrhagic disorders, bleeding diathesis, or coagulopathy (group 1)
• No bleeding > grade 2 or any bleeding requiring intervention within the past 4 weeks (group 1)
• No history of gross hemoptysis (defined as > ½ teaspoon of bright red blood) (group 1)
• Urine protein:creatinine (UPC) ratio < 1.0 by spot urinalysis
• For UPC ratio > 0.5, a 24-hour urine protein must be obtained and the urine protein level must be < 1,000 mg (group 1)
• None of the following conditions (group 1):
• Grade II or greater peripheral vascular disease
• Abdominal fistula
• Gastrointestinal perforation
• Intra-abdominal abscess
• No known hypersensitivity to any component of bevacizumab (group 1)
• No history of hypertensive crisis or hypertensive encephalopathy (group 1)

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since prior major surgical procedure
• More than 7 days since prior minor surgical procedure
• No prior chemotherapy for advanced NSCLC
• Postoperative adjuvant chemotherapy for previously resected NSCLC allowed if last dose was given > 1 year ago
• More than 3 weeks since prior radiation therapy and recovered
• More than 3 weeks since prior immunotherapy and/or hormonal therapy (not including hormone replacement therapy or contraceptives) and recovered
• More than 14 days since prior enzyme inducing anti-epileptic drugs (EIAEDs)
• More than 10 days since prior and no concurrent daily treatment with acetylsalicylic acid (> 325 mg/day) or NSAIDs known to inhibit platelet function for chronic conditions (group 1)
• No concurrent major surgical procedure (group 1)
• No concurrent carbamazepine, phenobarbital, or phenytoin
• No concurrent therapeutic anticoagulation (group 1)
• Prophylactic anticoagulation of venous access devices is allowed
• No concurrent treatment with dipyridamole, ticlopidine, clopidogrel, or cilostazol (group 1)
• No concurrent combination antiretroviral therapy for HIV-positive patients