The study consists of an open-label, Part 1 safety run-in (consisting of 1 to 3 cohorts of 9 subjects each), to confirm the safety of the regorafenib/ruxolitinib combination in subjects with relapsed or refractory metastatic colorectal cancer (CRC). If determined to be tolerable, Part 2 will proceed as a randomized, double-blind study evaluating ruxolitinib or placebo in combination with regorafenib in subjects with relapsed or refractory metastatic CRC previously treated with fluoropyrimidine, oxaliplatin, and/or irinotecan based chemotherapy, an anti-vascular endothelial growth factor (VEGF) therapy and if Kirsten rat sarcoma (KRAS) wild type an anti-epidermal growth factor receptor (EGFR) therapy.
Subjects in the safety run-in will receive open-label ruxolitinib and regorafenib; for the randomized, double-blind portion of the study all subjects will receive regorafenib and either ruxolitinib or placebo in a 1:1 blinded manner. Treatment for all subjects will consist of repeating 28-day cycles. Regorafenib will be self-administered for the first 21 days of each cycle, and ruxolitinib/placebo will be self-administered during the entire 28-day cycle. Treatment cycles will continue as long as the regimen is tolerated, and the subject does not meet the discontinuation criteria. When subjects discontinue regorafenib, ruxolitinib or placebo they will remain in the study and be followed for subsequent treatment regimens which are initiated and survival.