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

February 7, 2024 updated by: University Health Network, Toronto

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

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

155

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G2M9
        • Recruiting
        • Princess Margaret Cancer Centre
        • Contact:
        • Principal Investigator:
          • Eric Chen, MD
      • Toronto, Ontario, Canada, M4N 3M5
        • Not yet recruiting
        • Sunnybrook Odette Cancer Centre
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Time Frame: Start of study treatment to end of study, up to 48 months.
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
Time Frame: Start of study treatment to time of disease progression, up to 48 months.
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
Time Frame: Start of study treatment to time of death, up to 48 months.
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
Time Frame: Start of study treatment to end of study, up to 48 months.
Number of adverse events per grade
Start of study treatment to end of study, up to 48 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Eric Chen, MD, Princess Margaret Cancer Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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)

February 9, 2024

Last Update Submitted That Met QC Criteria

February 7, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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