Randomized Phase II Trial of 5-Fluorouracil/Leucovorin (5FU/LV) in Combination With Regorafenib in Patients With Metastatic Colorectal Cancer
The Methodist Hospital Research Institute
Summary
This is a non-inferiority randomized phase II trial investigating the efficacy and safety of 5FU/LV in combination with regorafenib for patients with metastatic colorectal cancer in the third-line setting. Patients will be randomly assigned in a 2:1 ratio between 5FU/LV combined with regorafenib or trifluridine-tipiracil (FTD-TPI) plus bevacizumab. Arm 1 (Treatment Arm) will consist of the 5FU/LV administered to 38 patients as (LV \[400 mg/m² IV over 120 minutes\], followed by 5FU \[400 mg/m² IV bolus then 2400 mg/m² IV infusion over 46 hours\] in 2-week cycles) and regorafenib will be administered dose of 80-120 mg per day with weekly 40 mg per day increases to a maximum of 120 mg per day for 3 weeks on /1 week off until disease progression, up to 12 cycles of treatment. Arm 2 (Control Arm) received by an additional 19 patients, will be given as FTD-TPI, administered orally, BID, at a starting dose of 35 mg/m2 of body-surface area, on days 1 through 5 and on days 8 through 12 every 28 days. Bevacizumab, at a dose of 5 mg per kilogram of body weight, will be administered intravenously on days 1 and 15. The 28-day treatment cycle continued until disease progression or unacceptable toxic effects occurred or consent was withdrawn, up to 12 cycles of treatment.
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Male or female ≥18 years of age. 2. Histopathological or cytologically confirmed metastatic CRC. 3. Failed second-line therapy for metastatic disease. 4. A minimum of one measurable disease per RECISTv1.1. 5. ECOG performance status of 0-2. 6. Life expectancy ≥6 months per treating physician or principal investigator. 7. Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure. 8. Adequate bone marrow, liver and renal fu…
Interventions
- DrugRegorafenib (BAY 73-4506)
Regorafenib will be administered a starting dose of 80 mg per day with weekly 40 mg per day increases to a maximum of 120 mg per day for 3 weeks on / 1 week off continued until disease progression or unacceptable toxic effects occurred or consent was withdrawn, up to 12 cycles of treatment.
- Drug5FU/LV
5FU/LV administered as (LV \[400 mg/m² IV over 120 minutes\], followed by 5FU \[400 mg/m² IV bolus then 2400 mg/m² IV infusion over 46 hours\] in 2-week cycles)
- DrugBevacizumab
Bevacizumab, at a dose of 5 mg per kilogram of body weight, will be administered intravenously on days 1 and 15.
- DrugTrifluridine-tipiracil
FTD-TPI, administered orally, BID, at a starting dose of 35 mg/m2 of body-surface area, on days 1 through 5 and on days 8 through 12 every 28 days.
Location
- Houston Methodist Neal Cancer CenterHouston, Texas