Conditions: Colorectal Cancer
Keywords: stage IV colon cancer stage IV rectal cancer recurrent colon cancer recurrent rectal cancer
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 38
Healthy volunteers: no

Brief 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.

Detailed description:
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.

Arms:
arm 1: Arm A: FOLFOX6 + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 5 mg/kg in 100 cc Normal Saline every 14 days on day one.

Drug: hydroxychloroquine hydroxychloroquine 200 mg po BID daily arm 2: Arm B: XELOX + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 7.5 mg/kg in 100 cc Normal Saline every 21 days.

Drug: hydroxychloroquine hydroxychloroquine 200 mg po BID daily

Interventions: intervention 1: hydroxychloroquine
Intervention descriptions: intervention 1: hydroxychloroquine 200 mg po BID daily

Protocol document: