A Multicenter Phase 1 Study of Intravenous Administration of REOLYSIN® (Reovirus Type 3 Dearing) in Combination With Irinotecan/Fluorouracil/Leucovorin (FOLFIRI) in Patients With KRAS Mutant Metastatic Colorectal Cancer
Reovirus Serotype 3 - Dearing Strain (REOLYSIN) is a naturally occurring, ubiquitous,
non-enveloped human reovirus. Reovirus has been shown to replicate selectively in
Ras-transformed cells causing cell lysis. Activating mutations in ras or mutation in
oncogenes signaling through the ras pathway may occur in as many as 80% of human tumors. The
specificity of the reovirus for Ras-transformed cells, coupled with its relatively
nonpathogenic nature in humans, makes it an attractive anti-cancer therapy candidate.
Eligible patients for this study include those with histologically confirmed cancer of the
colon or rectum with Kras mutation and measurable disease.
Cetuximab and panitumumab have shown to be ineffective in patients whose tumors have a KRAS
mutation. Therefore, currently, for patients with a KRAS mutation, the only option after
failure of front-line therapy is irinotecan or FOLFIRI, and there is no drug that can be
combined with it to improve clinical outcomes.
The trial is a Phase I dose escalation study with four dose levels, comprising cohorts of
three to six patients, to determine a maximum tolerated dose and dose-limiting toxicities
with the combination of REOLYSIN and FOLFIRI. FOLFIRI will be administered on the first day
of a two week (14-day) cycle, while REOLYSIN will be administered on days one through five
of a four week (28-day) cycle.
The study is expected to enroll 12 to 20 patients.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose limiting toxicity to define maximum tolerated dose and recommended Phase 2 dose
During the first cycle of treatment (4 week cycle)
United States: Food and Drug Administration
|The Ohio State University||Columbus, Ohio 43210|
|Montefiore Medical Center/Albert Einstein College of Medicine||Bronx, New York 10461|
|New York Presbyterian Hospital/ Weill Cornell Medical College||New York, New York 10065|