Ras-mutated Metastatic Colorectal Cancer, mCRC, MSS Metastatic Colorectal Cancer
Conditions
Brief summary
This is an open-label, randomized, multicenter Phase 2 study to assess the efficacy and safety of FOLFIRI + bevacizumab + pelareorep vs. FOLFIRI + bevacizumab in patients with RAS-mutated, MSS mCRC who have progressed after one prior line of oxaliplatin-based therapy.
Detailed description
Approximately 60 patients will be randomized 1:1 to the following study arms: * Arm A: FOLFIRI + bevacizumab + pelareorep * Arm B: FOLFIRI + bevacizumab The primary endpoint is ORR as assessed by the investigator per RECIST 1.1. OS, PFS, and assessment of the safety and tolerability of the study treatment combinations are secondary endpoints. The primary endpoint analysis will be performed after all patients have had at least one tumor assessment following initiation of study treatment or have progressed. The secondary endpoint analyses will take place at EOS.
Interventions
DRUGBevacizumab
Bevacizumab (5 mg/kg) IV infusion
DRUGFOLFIRI
irinotecan (180mg/m2), leucovorin 400 mg/m2 ± 5-FU (400 mg/m2) IV infusion
DRUGPelareorep
pelareorep 4.5 x 10\^10 TCID50 IV infusion
Sponsors
Oncolytics Biotech
Study design
Allocation
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 cancer of the colon or rectum with documented metastasis * Measurable disease per RECIST v. 1.1 * Not candidates for curative surgery or curative radiation * Progressed on, or been intolerant to, a first-line, oxaliplatin-based chemotherapy regimen in the metastatic setting or relapsed within 6 months of completing adjuvant oxaliplatin * Considered medically eligible to receive standard of care (SOC) FOLFIRI with bevacizumab * Non-microsatellite instability high or non-deficient mismatch repair (non-MSI-H/non dMMR) tumor status per a standard local testing method * Tumor confirmed to harbor a known RAS mutation per a standard local testing method * ECOG performance status of 0 or 1 * Patients must have adequate hematological, renal, and hepatic function * Female patients of childbearing potential must have a negative pregnancy test * Life expectancy of at least 6 months
Exclusion criteria
* Undergone systemic chemotherapy, radiotherapy, or surgery, \<4 weeks before study treatment * Ongoing AEs of Grade ≥2 that are related to anti-cancer treatment * Prior treatment with irinotecan * Symptomatic brain metastases * Active autoimmune disease * Receiving immunosuppressive or myelosuppressive medications * Active, uncontrolled infections * Known HIV infection or active hepatitis B or C that requires anti-viral treatment * History of another primary cancer within the last 3 years except for non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ * History of allergy or known hypersensitivity to any of the study drugs, study drug classes, * Uncontrolled or severe cardiac disease * Received any vaccine within 28 days prior to first study treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | At week 8 | Proportion of patients with complete response \[CR\], partial response \[PR\] assessed by the investigators and/or central reader according to RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) - | From the date of randomization through long term follow up at two years | OS defined as the time from date of randomization to death from any cause |
| Progression Free Survival (PFS) | From randomization to objective progression or death from any cause, whichever occurs first, up to two years | Time from randomization to the date of investigator-determined objective progression (according to RECIST 1.1) or death from any cause, whichever occurs first. |
| Disease Control Rate (DCR) | From randomization to disease progression or death from any cause, whichever occurs first, up to two years | Overall DCR, defined as the number of patients with a best overall response of CR, PR, or SD according to RECIST v. 1.1 |
| Duration of Response (DOR) | From randomization to disease progression or death from any cause, whichever occurs first, up to two years | Time from documentation of the first CR or PR to the time of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death. |
Countries
United States
Contacts
CONTACTName: Reference Study ID Number: REO 033
Outcome results
None listed