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

Metastatic Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05843188
• Other study ID #: Targeting DTP in mCRC
• Secondary ID: 22-5689
• Status: Recruiting
• Phase: Phase 2
• Start date: August 9, 2023
• Est. completion date: October 24, 2026

Study information

• Verified date: February 2024
• Source: University Health Network, Toronto
• Contact: Eric Chen, MD
• Phone: 416-946-263
• Email: eric.chen[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 155
• Est. completion date: October 24, 2026
• Est. primary completion date: April 24, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Hydroxychloroquine
Anti-Inflammatory - antimalarial - aminoquinolines
• Irinotecan
Antineoplastic agent
• Leucovorin
Folic acid derivative
• Fluorouracil
Antineoplastic agent
• Bevacizumab
Antineoplastic agent

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Odette Cancer Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	Overall survival	Average length of time that participants are alive.	Start of study treatment to time of death, up to 48 months.
Secondary	Incidences and severity of adverse events	Number of adverse events per grade	Start of study treatment to end of study, up to 48 months.