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

A Phase II Study of 5-FU, Irinotecan, Bevacizumab and Hydroxychloroquine in Drug-Tolerant Persister (DTP)-Selected Patients With Metastatic Colorectal Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Hydroxychloroquine; Drug: Irinotecan; Drug: Leucovorin; Drug: Fluorouracil; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 155
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Odette Cancer Centre
    • Toronto, Ontario, Canada, M5G2M9
      • Princess Margaret Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Hydroxychloroquine; Anti-Inflammatory - antimalarial - aminoquinolines; Drug: Irinotecan; Antineoplastic agent; Drug: Leucovorin; Folic acid derivative; Other Names: Folinic acid; Drug: Fluorouracil; Antineoplastic agent; Other Names: 5-FU; Drug: Bevacizumab; Antineoplastic agent
Active Comparator: 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	Drug: Irinotecan; Antineoplastic agent; Drug: Leucovorin; Folic acid derivative; Other Names: Folinic acid; Drug: Fluorouracil; Antineoplastic agent; Other Names: 5-FU; Drug: Bevacizumab; Antineoplastic agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Percentage of participants who have a partial response or complete response to study treatment.	Start of study treatment to end of study, up to 48 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Average length of time that participants' diseases do not worsen.	Start of study treatment to time of disease progression, up to 48 months.
Overall survival	Average length of time that participants are alive.	Start of study treatment to time of death, up to 48 months.
Incidences and severity of adverse events	Number of adverse events per grade	Start of study treatment to end of study, up to 48 months.

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Eric Chen, MD, Princess Margaret Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2023
• Primary Completion (Estimated): April 24, 2026
• Study Completion (Estimated): October 24, 2026

Study Registration Dates

• First Submitted: March 29, 2023
• First Submitted That Met QC Criteria: April 24, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Quinolines; Aminoquinolines; Chloroquine; Bevacizumab; Irinotecan; Fluorouracil; Hydroxychloroquine; Leucovorin
• Other Study ID Numbers: Targeting DTP in mCRC; 22-5689 (Other Identifier: University Health Network)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No