Regorafenib dose optimization study (ReDOS): A phase II randomized study of lower starting dose regorafenib compared to standard dose regorafenib in patients with refractory metastatic colorectal cancer (mCRC).

TPS3630Background: Regorafenib is an oral multikinase inhibitor that blocks several protein kinases involved in angiogenesis and oncogenesis. It was recently shown to provide a survival benefit in refractory metastatic colorectal cancer. Despite the observed benefits, toxicities such as palmar-plantar erythrodysesthesia syndrome (PPES- which occurs early in the first 1-2 weeks) and fatigue have limited its use. Multiple practices across the US adopted various dosing or interval scheduling despite the absence of supportive data. Methods: ReDOS (NCT02368886) is an Academic and Community Cancer Research United (ACCRU) network-led randomized phase II study of lower dose regorafenib compared to standard dose regorafenib in patients with refractory mCRC. Patients are randomized 1:1 to receive an escalating dose (Arm A: 80 mg daily Week 1, 120 mg daily Week 2,160 mg daily week 3 then 1 week off followed by Cycle 2) vs. standard dose (Arm B: 160 mg daily for 21 days/then 1 week off). Within each treatment arm, pa...