Study of REOLYSIN® in Combination With FOLFIRI and Bevacizumab in FOLFIRI Naive Patients With KRAS Mutant Metastatic Colorectal Cancer
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.
KRAS Mutant Metastatic Colorectal Cancer
Drug: Fluorouracil (5-FU)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Dose limiting toxicity to define maximum tolerated dose and recommended Phase 2 dose [ Time Frame: During the first cycle of treatment (4 week cycle) ] [ Designated as safety issue: Yes ]
- Pharmacokinetic parameters for irinotecan and 5-FU when combined with REOLYSIN® [ Time Frame: During the first cycle of treatment (4 week cycle) ] [ Designated as safety issue: No ]
- CEA and Objective Response, Clinical Benefit Rate (PR, CR, SD), progression-free survival, and overall survival (PFS and OS) [ Time Frame: Assessed every 8 weeks until disease progression or death ] [ Designated as safety issue: No ]
- Safety and tolerability of REOLYSIN® when administered in combination with FOLFIRI and bevacizumab [ Time Frame: During study and within 30 days of the last dose of REOLYSIN ] [ Designated as safety issue: Yes ]
- Correlative studies including determination of specific genetic mutations and aberrant signalling pathways from tumor tissue to identify novel biomarkers of response and efficacy [ Time Frame: During and within 30 days of the last dose of REOLYSIN® ] [ Designated as safety issue: No ]
- In vitro studies in human-derived colorectal cancer cells including the isogenic cell lines, to study the mechanism and scientific basis of synergy between irinotecan and reovirus [ Time Frame: During study and within 30 days of the last dose of REOLYSIN® ] [ Designated as safety issue: No ]
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||October 2015|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01274624
|United States, New York|
|Montefiore Medical Center/Albert Einstein College of Medicine||Recruiting|
|Bronx, New York, United States, 10461|
|Contact: Mohammed Ghalib, MD 718-405-8515 firstname.lastname@example.org|
|Principal Investigator: Sanjay Goel, MD|
|New York Presbyterian Hospital/ Weill Cornell Medical College||Recruiting|
|New York, New York, United States, 10065|
|Contact: June Greenberg 212-746-2651 email@example.com|
|Principal Investigator: Alison Ocean, MD|
|United States, Ohio|
|The Ohio State University||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Tanios Bekaii-Saab, MD 614-293-4372 Tanios.Saab@osumc.edu|
|Principal Investigator: Tanios Bekaii-Saab, MD|