Conditions: Colorectal Cancer Metastatic
Keywords: Metastatic Colorectal Cancer K-RAS mutation BRAF mutation Regorafenib BAY 73-4506 FOLFIRI Irinotecan 5-FU Leucovorin Placebo Phase II Multi-Center Randomized Lineberger North Carolina Cancer Hospital UNC
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 181
Healthy volunteers: no

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.

Arms:
arm 1: regorafenib 160 mg + FOLFIRI arm 2: Placebo + FOLFIRI

Interventions: intervention 1: Regorafenib (BAY 73-4506) intervention 2: FOLFIRI intervention 3: Placebo intervention 4: FOLFIRI
Intervention descriptions: intervention 1: Regorafenib, 160 mg, PO, Days 4-10 and Days 18-24 of 28 day cycle intervention 2: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle. intervention 3: Placebo, 160 mg, PO, Days 4-10 and Days 18-24 of 28 day cycle intervention 4: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Protocol document: