Study of REOLYSIN® in Combination With FOLFIRI and Bevacizumab in FOLFIRI Naive Patients With KRAS Mutant Metastatic Colorectal Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01274624|
Recruitment Status : Completed
First Posted : January 11, 2011
Last Update Posted : December 19, 2018
|Condition or disease||Intervention/treatment||Phase|
|KRAS Mutant Metastatic Colorectal Cancer||Biological: REOLYSIN® Drug: Irinotecan Drug: Leucovorin Drug: Fluorouracil (5-FU) Drug: Bevacizumab||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||December 2010|
|Actual Primary Completion Date :||February 2018|
|Actual Study Completion Date :||November 2018|
- Biological: REOLYSIN®
1 hour intravenous infusion administered on Days 1, 2, 3, 4, and 5 every 4 weeks.Other Name: Reovirus serotype 3 Dearing Strain
- 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.
- Dose limiting toxicity to define maximum tolerated dose and recommended Phase 2 dose [ Time Frame: During the first cycle of treatment (4 week cycle) ]
- Pharmacokinetic parameters for irinotecan and 5-FU when combined with REOLYSIN® [ Time Frame: During the first cycle of treatment (4 week cycle) ]
- 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 ]
- 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 ]
- 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® ]
- 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® ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01274624
|United States, New York|
|Montefiore Medical Center/Albert Einstein College of Medicine|
|Bronx, New York, United States, 10461|
|New York Presbyterian Hospital/ Weill Cornell Medical College|
|New York, New York, United States, 10065|