Metastatic Colorectal Cancer
Conditions
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.
Interventions
DRUGHydroxychloroquine
Anti-Inflammatory - antimalarial - aminoquinolines
DRUGIrinotecan
Antineoplastic agent
DRUGLeucovorin
Folic acid derivative
DRUGFluorouracil
Antineoplastic agent
DRUGBevacizumab
Antineoplastic agent
Sponsors
University Health Network, Toronto
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 0-1. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATOREric Chen, MD
Princess Margaret Cancer Centre
Outcome results
None listed