NCT01274624

Study of REOLYSIN® in Combination With FOLFIRI and Bevacizumab in FOLFIRI Naive Patients With KRAS Mutant Metastatic Colorectal Cancer

A Multicenter Phase 1 Study of Intravenous Administration of REOLYSIN® (Reovirus Type 3 Dearing) in Combination With Irinotecan/Fluorouracil/Leucovorin (FOLFIRI) and Bevacizumab in FOLFIRI Naive Patients With KRAS Mutant Metastatic Colorectal Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: Oncolytics Biotech · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 1 dose-escalation study with three dose levels to determine the maximum tolerated dose of REOLYSIN® combined with FOLFIRI and bevacizumab.

Detailed description

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.

Conditions

• KRAS Mutant Metastatic Colorectal Cancer

Interventions

Type	Name	Description
BIOLOGICAL	REOLYSIN®	1 hour intravenous infusion administered on Days 1, 2, 3, 4, and 5 every 4 weeks.
DRUG	Irinotecan	90-minute intravenous infusion on Day 1 every 2 weeks. Dose levels of 125 mg/m2, 150 mg/m2, 150 mg/m2, 180 mg/m2.
DRUG	Leucovorin	2-hour infusion of 400 mg/m2 on Day 1 every 2 weeks.
DRUG	Fluorouracil (5-FU)	400 mg/m2 intravenous bolus followed by 2400 mg/m2 as a continuous intravenous infusion over 46 hours administered on Day 1 every 2 weeks.
DRUG	Bevacizumab	30, 60 or 90 minute infusion on Day 1 every 2 weeks. Dose level 5 mg/kg.

Timeline

• Start date: 2010-12-01
• Primary completion: 2018-02-01
• Completion: 2018-11-01
• First posted: 2011-01-11
• Last updated: 2018-12-19

Locations

2 sites across 1 country: United States