Hydroxychloroquine, Carboplatin, Paclitaxel, and Bevacizumab in Recurrent Advanced Non-Small Cell Lung Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced non-small cell lung cancer, meeting the following criteria:
• Recurrent disease
• No component of squamous cell carcinoma
• Mixed tumors will be categorized by predominant cell type
• No mixed histology with small cell component
• Diagnosis established on metastatic tumor aspirate or biopsy (not sputum cytology alone) and meets 1 of the following staging criteria:
• Stage IIIB disease with malignant pleural effusion
• Stage IV disease
• Measurable disease
• More than 1 year since post-operative adjuvant therapy for previously resected non-small cell lung cancer with evidence of disease progression
• No known CNS metastases by CT scan or brain MRI within the past 28 days

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 2 times ULN and no other liver function test abnormality in patients with Gilbert disease)
• AST/ALT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)
• Alkaline phosphatase ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
• INR ≤ 1.5 and aPTT normal
• Urine protein:creatinine ratio < 1.0 OR urine protein ratio < 1,000 mg by 24-hour urine collection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No ongoing or active infection
• No psoriasis or porphyria
• No HIV positivity
• No significant traumatic injury within the past 28 days
• No serious non-healing wound, ulcer, or bone fracture
• No peripheral or sensory neuropathy > grade 1
• No hypertension that cannot be controlled by antihypertensive medication (i.e., blood pressure > 150/100 mm Hg despite optimal medical therapy)
• No cardiovascular disease, including any of the following:
• Unstable angina
• New York Heart Association class II-IV congestive heart failure
• History of significant vascular disease (e.g., aortic aneurysm)
• Symptomatic peripheral vascular disease within the past 6 months
• Myocardial infarction within the past 6 months
• Stroke within the past 6 months
• No other active malignancy within the past 3 years, except curatively treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or ductal or lobular carcinoma in situ of the breast, or other curatively treated malignancy with no evidence of disease > 3 years
• No retinal or visual field changes from prior 4-aminoquinoline compound therapy
• No known hypersensitivity to 4-aminoquinoline compound
• No known glucose-6-phosphate (G-6P) deficiency
• No known bleeding diathesis or coagulopathy
• No known gastrointestinal pathology that would interfere with drug bioavailability
• No known prior hypersensitivity to carboplatin, paclitaxel, bevacizumab, hydroxychloroquine, or any of their components
• No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• No history of gross hemoptysis (i.e., bright red blood of a ½ teaspoon or more) within the past 3 months
• No history of any social or medical condition that, in the investigator's opinion, might interfere with the patient's ability to comply with the protocol or pose additional or unacceptable risk to the patient

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 2 weeks since prior radiation to sites other than the brain, and recovered to ≤ grade 1
• At least 28 days since prior and no concurrent full-dose anticoagulants or thrombolytic agents
• At least 28 days since prior major surgical procedure or open biopsy and no anticipated need for such during study therapy
• Vascular access device placement with wound recovery allowed before study
• No prior cytotoxic chemotherapy or targeted therapy in the advanced or metastatic setting
• No concurrent treatment for rheumatoid arthritis or systemic lupus erythematosus
• No concurrent combination antiretroviral therapy
• No concurrent hydroxychloroquine for treatment or prophylaxis of malaria
• No concurrent aurothioglucose
• No other concurrent investigational or commercial agent or therapy for this malignancy