Study of Hydroxychloroquine With FOLFIRI and Bevacizumab in DTP-high Metastatic Colorectal Cancer

Inclusion Criteria: Histologically confirmed colorectal cancer, not amenable to curative resection. Microsatellite stable/mismatch repair proficient (MSS/pMMR) colorectal cancer. No prior systemic therapy for metastatic disease. Evaluable disease based on RECIST 1.1 criteria. Adequate hematological, hepatic and renal functions Eastern Cooperative Oncology Group (ECOG) Performance status 0-1. Estimated life expectancy of > 6 months. Negative pregnancy test for female patients with child-bearing potential. No history of retinal disorder. No history of glucose-6-phosphate dehydrogenase deficiency (G6PD) . Considered to be DTP-signature high to receive HCQ treatment Exclusion Criteria: Women who are pregnant or nursing. Have received radiotherapy, chemotherapy, biological therapy, or investigational treatment less than four weeks (six weeks for nitrosoureas or mitomycin C) prior to first dose of FOLFIRI-beva or have not recovered from all acute toxicities from prior treatments to grade 1 or less, with the exception of alopecia and those deemed not to affect safety assessment. Have concurrent malignancy with exception of malignancy that was treated curatively and without evidence of recurrence within 3 years of study enrollment, or fully resected basal or squamous cell skin cancer and any carcinoma in situ which are considered to be of low risk of recurrence. Have had major surgery within 28 days of study enrollment. Placement of a venous access device within 28 days of starting therapy is allowed. Have any medical condition that would impair the administration of oral agents including significant bowel resection, inflammatory bowel disease or uncontrolled nausea or vomiting. Known central nervous system metastasis. Patients with history of central nervous system metastases are eligible if they are clinically and radiographically stable for at least 3 months and not taking steroids or anticonvulsants.