Hydroxychloroquine, Capecitabine, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed colorectal carcinoma

  • Metastatic disease
• Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as > 20 mm by conventional techniques or > 10 mm by spiral CT scan
• Brain metastases allowed provided they have been treated and stable for > 4 weeks

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• AST/ALT ≤ 3 times upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 times ULN
• PT (INR) ≤ 1.5
• Creatinine < 1.5 times ULN
• Creatinine clearance ≥ 30 mL/min
• Urine protein:creatinine ratio < 1.0 OR < 1 g protein by 24-hour urine collection
• Not on dialysis
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception before, during, and for 4 weeks after completion of study treatment
• Prior non-colonic malignancies allowed provided there is no current clinical evidence of persistent or recurrent disease AND the patient is not on active therapy, including hormonal therapy
• No uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg, despite antihypertensive medications

• No cardiac disease, including any of the following:

  • NYHA class III-IV congestive heart failure
  • Unstable angina (anginal symptoms at rest)
  • New onset angina (began within the past 3 months)
  • Myocardial infarction within the past 6 months
  • Uncontrolled arrhythmia
• No thrombolic or embolic events (e.g., cerebrovascular accident including transient ischemic attacks) within the past 6 months
• No serious non-healing wound, ulcer, or bone fracture
• No significant traumatic injury within the past 28 days
• No neuropathy ≥ grade 2
• No evidence of bleeding diathesis or coagulopathy
• No condition that would impair the patient's ability to swallow whole pills
• No malabsorption problem
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• No known G-6PD deficiency
• No retinal or visual field changes from prior 4-aminoquinoline compound use
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to capecitabine or hydroxychloroquine
• No other concurrent serious systemic disorders (including active infections) that, in the investigator's opinion, would compromise the safety of the patient or compromise the patient's ability to complete the study

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior chemotherapy for metastatic disease, except for adjuvant therapy that was completed ≥ 6 months before the first evidence of metastasis
• More than 28 days since prior major surgical procedure or open biopsy

• No concurrent anticoagulation with warfarin

  • Concurrent low molecular weight heparin (or an equivalent drug) allowed
• No concurrent hydroxychloroquine for treatment or prophylaxis of malaria
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent St. John wort
• No other concurrent investigational or anticancer agents or therapies