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)
18 Years
N/A
Both
Colorectal Cancer
Trial Information
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)
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression-free survival
Outcome Time Frame:
4 years
Safety Issue:
No
Principal Investigator
Rebecca A. Moss, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Cancer Institute of New Jersey
Authority:
United States: Institutional Review Board
Study ID:
070806
NCT ID:
NCT01006369
Start Date:
May 2009
Completion Date:
May 2014
Related Keywords:
- Colorectal Cancer
- stage IV colon cancer
- stage IV rectal cancer
- recurrent colon cancer
- recurrent rectal cancer
- Colorectal Neoplasms
Name | Location |
|---|---|
| Cancer Institute of New Jersey at Hamilton | Hamilton, New Jersey 08690 |
| Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School | New Brunswick, New Jersey 08903 |
| New Jersey Medical School/The University Hospital Cancer Center | Newark, New Jersey 07103 |
