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Autophagy and Anti-Angiogenesis in Metastatic Colorectal Carcinoma: A Phase II Trial of Hydroxychloroquine to Augment Effectiveness of XELOX-Bevacizumab. A Study of the Cancer Institute of New Jersey Oncology Group (CINJOG)
| City: |
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Hamilton |
| State: |
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New Jersey |
| Zip Code: |
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08690 |
| Conditions: |
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Colorectal Cancer |
| Purpose: |
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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.
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| Study Summary: |
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OBJECTIVES:
Primary
- To assess the progression-free survival (PFS) of patients with metastatic colorectal
carcinoma treated with hydroxychloroquine in combination with capecitabine,
oxaliplatin, and bevacizumab and to compare this to a previously reported median PFS of
7.9 months.
Secondary
- To measure the overall response rate.
- To measure the duration of response for responding patients.
- To measure the disease-control rate (complete response, partial response, or stable
disease for at least 2 courses).
- To document the safety and feasibility of this regimen in these patients.
- To develop surrogate biomarkers for autophagy detection in patient tissue specimens and
to characterize the effects of hydroxychloroquine on autophagy in patients in vivo.
OUTLINE: This is a multicenter study.
Patients receive bevacizumab IV over 30-90 minutes and oxaliplatin IV over 2 hours on day 1.
Patients also receive oral capecitabine twice daily on days 1-15 and oral hydroxychloroquine
twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression
or unacceptable toxicity.
Peripheral blood and tumor tissue samples may be collected for biomarker and other
laboratory studies.
After completion of study treatment, patients are followed up for 1 year.
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| Criteria: |
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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
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| NCT ID: |
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NCT01006369 |
| Primary Contact: |
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Principal Investigator
Rebecca A. Moss, MD
Cancer Institute of New Jersey
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| Backup Contact: |
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N/A |
| Location Contact: |
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Hamilton, New Jersey 08690
United States
Clinical Trials Office - Cancer Institute of New Jersey at Ham
Phone: 609-631-6946
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 24, 2013 |
| Modifications to this listing: |
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