Intervention: Hydroxychloroquine
Trial phase: Phase 2
ATC code: P01BA02
SMILES: CCN(CCO)CCCC(C)Nc1ccnc2cc(Cl)ccc12
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 25
Group description: bevacizumab: Arm A: FOLFOX6 + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 5 mg/kg in 100 cc Normal Saline every 14 days on day one

Arm B: XELOX + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 7.5 mg/kg in 100 cc Normal Saline every 21 days

XELOX regimen: Capecitabine will be started at a dose of 1,000 mg/m2/day bid po (total daily dose = 2,000 mg/m2) for 14 days (28 doses) of the 21 day cycle. This cycle will be repeated every 21 days. Oxaliplatin will be started at a dose of 130 mg/m2, in 250 ml of D5W over 2 hours given day 1 of each cycle. This cycle will be repeated every 21 days.

hydroxychloroquine: hydroxychloroquine 200 mg po BID daily
Eligibility criteria:
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