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

University Health Network, Toronto

Status and phase: Active, not recruiting; Phase 2

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: Leucovorin; Drug: Hydroxychloroquine; Drug: Irinotecan; Drug: Fluorouracil; Drug: Bevacizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT05843188

22-5689 (Other Identifier)

Targeting DTP in mCRC

Details and patient eligibility

About

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.

Enrollment: 155 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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155 participants in 2 patient groups

High DTP-signature

Experimental group

Description:

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

Treatment:

Drug: Bevacizumab

Drug: Fluorouracil

Drug: Irinotecan

Drug: Hydroxychloroquine

Drug: Leucovorin

Low DTP-signature

Active Comparator group

Description:

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

Treatment:

Drug: Bevacizumab

Drug: Fluorouracil

Drug: Irinotecan

Drug: Leucovorin