Conditions: CRC (Colorectal Cancer)
Keywords: Metastatic Colorectal Cancer Colon Cancer Ruxolitinib adenocarcinoma regorafenib Jakavi ® Jakafi ® Stivarga ®
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 396
Healthy volunteers: no

Brief summary:
The purpose of this study was to determine if ruxolitinib, in combination with regorafenib, is safe and effective in the treatment of metastatic colorectal cancer.

Detailed description:
The study consisted 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 was to 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 received open-label ruxolitinib and regorafenib; for the randomized, double-blind portion of the study all subjects received regorafenib and either ruxolitinib or placebo in a 1:1 blinded manner. Treatment for all subjects consisted of repeating 28-day cycles. Regorafenib was self-administered for the first 21 days of each cycle, and ruxolitinib/placebo was self-administered during the entire 28-day cycle. Treatment cycles continued as long as the regimen is tolerated, and the subject does not meet the discontinuation criteria. When subjects discontinued regorafenib, ruxolitinib or placebo they remained in the study and were followed for subsequent treatment regimens which were initiated and survival.

Arms:
arm 1: None arm 2: None

Interventions: intervention 1: Ruxolitinib intervention 2: Regorafenib intervention 3: Placebo
Intervention descriptions: intervention 1: 5 mg tablets to be administered by mouth

Ruxolitinib 20 mg twice a day (BID) (Part 1) (NOTE: The starting dose for the randomized portion of study (Part 2) was 15 mg BID based on results from Part 1.) intervention 2: Regorafenib 160mg once daily for the first 21 days of each 28-day cycle. (NOTE: Dose interruptions and modifications for regorafenib are expected when toxicities occur in which dose interruptions or modifications are appropriate.) intervention 3: 5 mg matching placebo tablets to be administered by mouth

Protocol document: