Hydroxychloroquine, Capecitabine, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: hydroxychloroquine
Intervention description: hydroxychloroquine 200 mg po BID daily
Intervention MeSH terms: Hydroxychloroquine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage IV colon cancer; stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by stopping
      them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in
      different ways. Some block the ability of tumor cells to grow and spread. Others find tumor
      cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop
      the growth of tumor cells by blocking blood flow to the tumor. Hydroxychloroquine may help
      chemotherapy and bevacizumab work better and kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving hydroxychloroquine together with
      capecitabine, oxaliplatin, and bevacizumab works in treating patients with metastatic
      colorectal cancer.
    

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