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

NCT ID: NCT05843188

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 155 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-09
• Study Completion Date: 2026-10-24

Brief 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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

High DTP-signature

Take HCQ, 400 mg by mouth, twice daily. Receive FOLFIRI+bevacizumab (irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5-FU 2400 mg/m2 over 46 - 48 hours, bevacizumab 5 mg/kg), intravenously, every 2 weeks

Group Type: EXPERIMENTAL

Hydroxychloroquine

Intervention Type: DRUG

Anti-Inflammatory - antimalarial - aminoquinolines

Irinotecan

Intervention Type: DRUG

Antineoplastic agent

Leucovorin

Intervention Type: DRUG

Folic acid derivative

Fluorouracil

Intervention Type: DRUG

Antineoplastic agent

Bevacizumab

Intervention Type: DRUG

Antineoplastic agent

Low DTP-signature

Receive FOLFIRI+bevacizumab (irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5-FU 2400 mg/m2 over 46 - 48 hours, bevacizumab 5 mg/kg), intravenously, every 2 weeks

Group Type: ACTIVE_COMPARATOR

Irinotecan

Intervention Type: DRUG

Antineoplastic agent

Leucovorin

Intervention Type: DRUG

Folic acid derivative

Fluorouracil

Intervention Type: DRUG

Antineoplastic agent

Bevacizumab

Intervention Type: DRUG

Antineoplastic agent

Interventions

Hydroxychloroquine

Anti-Inflammatory - antimalarial - aminoquinolines

Intervention Type: DRUG

Irinotecan

Antineoplastic agent

Intervention Type: DRUG

Leucovorin

Folic acid derivative

Intervention Type: DRUG

Fluorouracil

Antineoplastic agent

Intervention Type: DRUG

Bevacizumab

Antineoplastic agent

Intervention Type: DRUG

Other Intervention Names

Folinic acid; 5-FU

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric Chen, MD

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Cancer Centre

Locations

Sunnybrook Odette Cancer Centre

Toronto, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

22-5689

Identifier Type: OTHER

Identifier Source: secondary_id

Targeting DTP in mCRC

Identifier Type: -

Identifier Source: org_study_id