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

• Status: Not yet recruiting
• Trial end date: 2026-10-24
• Target enrollment: 0
• Participant gender: All

Summary

This is a two arm, 2-center, Phase II, study of 5-FU, irinotecan, bevacizumab (FOLFIRI-beva) and hydroxychloroquine (HCQ) in patients with previously untreated metastatic colorectal cancer (mCRC).

Up to 155 patients will be screened for DTP-signature and up to 31 evaluable patients who are determined to be DTP-signature high will be treated with FOLFIRI-beva and HCQ.

Patients will continue to receive treatments until evidence of disease progression, intolerable side effects, withdrawal of consent or death.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Health Network, Toronto
• Treatments: Bevacizumab; Fluorouracil; Hydroxychloroquine; Irinotecan; Leucovorin

Criteria

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.