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.