Clinical trial NCT05843188: Study of Hydroxychloroquine With FOLFIRI and Bevacizumab in DTP-high Metastatic Colorectal Cancer
Official title: A Phase II Study of 5-FU, Irinotecan, Bevacizumab and Hydroxychloroquine in Drug-Tolerant Persister (DTP)-Selected Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2023-05-06
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate
timeFrame: Start of study treatment to end of study, up to 48 months.
Secondary outcomes:
measure: Progression-free survival
timeFrame: Start of study treatment to time of disease progression, up to 48 months.
measure: Overall survival
timeFrame: Start of study treatment to time of death, up to 48 months.
measure: Incidences and severity of adverse events
timeFrame: Start of study treatment to end of study, up to 48 months.
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Eric Chen, MD
role: PRINCIPAL_INVESTIGATOR
References: