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

NCT05843188 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: Targeting DTP in mCRC22-5689
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Progression-free survival

  Start of study treatment to time of disease progression, up to 48 months.

• Overall survival

  Start of study treatment to time of death, up to 48 months.

• Incidences and severity of adverse events

  Start of study treatment to end of study, up to 48 months.

Study Arms (2)

High DTP-signature

EXPERIMENTAL

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; Drug: Irinotecan; Drug: Leucovorin; Drug: Fluorouracil; Drug: Bevacizumab

Low DTP-signature

ACTIVE COMPARATOR

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; Drug: Leucovorin; Drug: Fluorouracil; Drug: Bevacizumab

Interventions

Hydroxychloroquine DRUG

Anti-Inflammatory - antimalarial - aminoquinolines

High DTP-signature

Irinotecan DRUG

Antineoplastic agent

High DTP-signature; Low DTP-signature

Leucovorin DRUG

Folic acid derivative

Also known as: Folinic acid

High DTP-signature; Low DTP-signature

Fluorouracil DRUG

Antineoplastic agent

Also known as: 5-FU

High DTP-signature; Low DTP-signature

Bevacizumab DRUG

Antineoplastic agent

High DTP-signature; Low DTP-signature

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (2)

Sunnybrook Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G2M9, Canada

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Hydroxychloroquine; Irinotecan; Leucovorin; Fluorouracil; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Eric Chen, MD

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: May 6, 2023
• Study Start: August 9, 2023
• Primary Completion: April 24, 2026
• Study Completion (Estimated): October 24, 2026
• Last Updated: December 9, 2025

Record last verified: 2025-12

Locations

CA (2)