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

Sponsor

University Health Network, Toronto (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05843188

Collaborator

(none)

155

Enrollment

Location

Arms

Anticipated Duration (Months)

3.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: Hydroxychloroquine Drug: Irinotecan Drug: Leucovorin Drug: Fluorouracil Drug: Bevacizumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

155 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Apr 24, 2023

Anticipated Primary Completion Date :

Apr 24, 2026

Anticipated Study Completion Date :

Oct 24, 2026

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall response rate [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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.