Regorafenib+FOLFIRI Versus Placebo+FOLFIRI as 2nd Line Tx in Metastatic Colorectal Cancer
- Conditions
- Colorectal Cancer Metastatic
- Interventions
- Registration Number
- NCT01298570
- Lead Sponsor
- UNC Lineberger Comprehensive Cancer Center
- Brief Summary
This randomized (2:1), multi-center, placebo-controlled, phase II efficacy study is designed to compare PFS between regorafenib + FOLFIRI chemotherapy (ARM A) versus placebo + FOLFIRI (ARM B) in patients with mCRC previously treated with a FOLFOX regimen.
- Detailed Description
This randomized (2:1 ratio), multi-center, placebo-controlled, phase II efficacy study is designed to compare progression-free survival (PFS) between regorafenib + FOLFIRI (5-fluorouracil + leucovorin + irinotecan \[ARM A\] versus placebo + FOLFIRI \[ARM B\]) in patients with metastatic colorectal carcinoma (mCRC) previously treated with a FOLFOX (5-fluorouracil + leucovorin + oxaliplatin) regimen. Secondary objectives include objective response (OR) rates, disease control (DC) rates, and overall survival (OS). A pharmacokinetic (PK) evaluation of irinotecan will be conducted in a subset of patients at selected sites. This trial also incorporates a number of exploratory analyses designed to evaluate potential correlations between blood and tissue biomarkers and clinical benefit.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 181
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + FOLFIRI Placebo Placebo + FOLFIRI Regorafenib + FOLFIRI FOLFIRI regorafenib 160 mg + FOLFIRI Placebo + FOLFIRI FOLFIRI Placebo + FOLFIRI Regorafenib + FOLFIRI Regorafenib (BAY 73-4506) regorafenib 160 mg + FOLFIRI
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) 5.5 years To compare PFS between regorafenib + FOLFIRI chemotherapy (ARM A) versus placebo + FOLFIRI (ARM B) in patients failing one prior oxaliplatin-containing regimen for metastatic colorectal cancer. PFS is defined as the time from randomization until metastatic colorectal cancer (mCRC) progression or death as a result of any cause. Radiographic response will be measured by RECIST, Response Evaluation Criteria In Solid Tumors Criteria, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
- Secondary Outcome Measures
Name Time Method Overall Response(OR)Rate 3 years To compare overall response (OR) rates (OR= CR + PR) between ARM A and ARM B as defined via Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Disease Control (DC) Rate 3 years To compare Disease Control (DC) Rate (DC= CR + PR + SD) between ARM A and ARM B as defined via Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions and Stable Disease (SD) ), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Overall Survival (OS) 5.5 years To compare overall survival (OS) between ARM A and ARM B. OS is defined as the time from randomization until death as a result of any cause.
Drug Metabolism 28 days To compare the pharmacokinetic (PK) profile of FOLFIRI between a subset of patients receiving regorafenib (ARM A) and patients receiving placebo (Arm B). The Area Under the Curve (AUC) levels of the irinotecan metabolite SN-38 were compared.
Percentage of Patients With Severe Adverse Events 3 years Toxicity Assessments were made according to NCI CTCAE v. 4.0 . Severe events (grades 3-4) that occurred in a higher percentage of regorafenib treated participants as compared to placebo are reported below.
Trial Locations
- Locations (24)
Portsmouth Naval Medical Center
🇺🇸Portsmouth, Virginia, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
University of Louisville James Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
Georgia Cancer Specialists
🇺🇸Atlanta, Georgia, United States
New York University Langone Medical Center
🇺🇸New York, New York, United States
Carolinas HealthCare System
🇺🇸Charlotte, North Carolina, United States
The Moses Cone Regional Cancer Center
🇺🇸Greensboro, North Carolina, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
North Shore Long Island Jewish Health System
🇺🇸Manhasset, New York, United States
Mount Sinai Medical Center-Miami
🇺🇸Miami, Florida, United States
Southeast Medical Oncology Center
🇺🇸Goldsboro, North Carolina, United States
Indiana University Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Ireland Cooperative Clinical Research Group
🇮🇪Dublin, Ireland
Wake Forest University Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
First Health of the Carolinas, Moore Regional Hospital
🇺🇸Pinehurst, North Carolina, United States
Multicare Regional Cancer Center
🇺🇸Tacoma, Washington, United States
Seby B. Jones Cancer Center
🇺🇸Boone, North Carolina, United States
Leo W. Jenkins Cancer Center at ECU Medical School
🇺🇸Greenville, North Carolina, United States
Rex Cancer Center at Rex Hospital
🇺🇸Raleigh, North Carolina, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States