A Phase II Study of 5-FU, Irinotecan, Bevacizumab and Hydroxychloroquine in Drug-Tolerant Persister (DTP)-Selected Patients With Metastatic Colorectal Cancer
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Enrollment
- 155
- Locations
- 4
- Primary Endpoint
- Overall response rate
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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-
- •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.
Arms & Interventions
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
Intervention: Leucovorin (Drug)
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
Intervention: Bevacizumab (Drug)
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
Intervention: Hydroxychloroquine (Drug)
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
Intervention: Irinotecan (Drug)
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
Intervention: Fluorouracil (Drug)
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
Intervention: Bevacizumab (Drug)
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
Intervention: Irinotecan (Drug)
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
Intervention: Leucovorin (Drug)
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
Intervention: Fluorouracil (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Progression-free survival(Start of study treatment to time of disease progression, up to 48 months.)
- Overall survival(Start of study treatment to time of death, up to 48 months.)
- Incidences and severity of adverse events(Start of study treatment to end of study, up to 48 months.)