Overview

This trial is active, not recruiting.

Condition metastatic colorectal cancer
Treatments ruxolitinib, regorafenib, placebo
Phase phase 2
Targets VEGF, KIT, PDGF, RET, JAK, RAF, JAK1, JAK2
Sponsor Incyte Corporation
Start date March 2014
End date February 2016
Trial size 407 participants
Trial identifier NCT02119676, INCB18424-267

Summary

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
ruxolitinib Jakafi ®
5 mg tablets to be administered by mouth Ruxolitinib 15mg BID (NOTE: Starting dose of randomized portion of study may be 10mg BID based on results from safety run-in study. Dose of ruxolitinib may be increased during randomized study, based on results from safety run-in.)
regorafenib Stivarga ®
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.)
(Active Comparator)
regorafenib Stivarga ®
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.)
placebo
5 mg matching placebo tablets to be administered by mouth

Primary Outcomes

Measure
Part 1: Determination of the dose of ruxolitinib that is safe and tolerable in combination with regorafenib as measured by the number of dose-limiting toxicities (DLTs) observed in the evaluation cohort
time frame: Baseline through Day 28
Part 2: Overall Survival (OS)
time frame: Randomization until death due to any cause. Approximately 28 months.]

Secondary Outcomes

Measure
Progression Free Survival (PFS)
time frame: Randomization through disease progression, or death due to any cause if sooner. Approximately 28 months.
Objective Response Rate
time frame: Baseline through end of study. Approximately 28 months.
Duration of Response
time frame: Baseline through end of study. 28 months.
Safety and tolerability of the treatment regimens assessed by a summary of adverse events and clinical laboratory assessments.
time frame: Baseline through approximately 30 days post treatment discontinuation. Approximately 28 months.
Disease Control
time frame: Baseline through end of study. Approximately 28 months.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic. - Previous treatment with fluoropyrimidine-, oxaliplatin- and irinotecan- based chemotherapy, an anti-VEGF therapy (if no contraindication) and if KRAS wild type and no contraindication, an anti-EGFR therapy. - Radiographically measurable or evaluable disease (per RECIST v1.1) - Life expectancy of ≥ 12 weeks. - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 - Three or more weeks have elapsed from the completion of previous treatment regimen and subjects must have recovered or be at a new stable baseline from any related toxicities. - Prior radiotherapy to disease sites is allowed with certain protocol-defined restrictions. Exclusion Criteria: - Prior treatment with regorafenib. - Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs. - Active peptic ulcer disease, inflammatory bowel disease (eg, ulcerative colitis, Crohn's disease), diverticulitis, or other gastrointestinal conditions with increased risk of perforation or gastrointestinal bleeding. - Recent history (≤ 3 months) or ongoing partial or complete bowel obstruction unless due to disease under study and corrected with surgery. - Blood pressure ≥ 140/90 mmHg. - Active bleeding diathesis or history of any major bleeding (eg, requiring transfusion of red blood cells (RBCs), central nervous system (CNS) bleeding, or significant hemoptysis within 6 months of enrollment. Subjects with bleeding secondary to underlying disease (including gastrointestinal (GI) perforation or fistula) that has been corrected by surgery or alternative procedure may be included.

Additional Information

Official title A Randomized, Double-Blind Study of Ruxolitinib or Placebo in Combination With Regorafenib in Subjects With Relapsed or Refractory Metastatic Colorectal Cancer
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Incyte Corporation.