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