Study of REOLYSIN® in Combination With FOLFIRI and Bevacizumab in FOLFIRI Naive 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. Over the past year, two randomized phase III trials have demonstrated that OS and PFS for these patients increase when bevacizumab is combined with the standard FOLFIRI therapy. 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®, bevacizumab, and FOLFIRI. FOLFIRI and bevacizumab 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 20 to 32 patients.