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Study of Ruxolitinib in Colorectal Cancer Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02119676
Recruitment Status : Terminated (Substudy 1 was terminated for futility at interim analysis and Substudy 2 was terminated per sponsor decision.)
First Posted : April 22, 2014
Results First Posted : June 14, 2017
Last Update Posted : February 13, 2018
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Tracking Information
First Submitted Date  ICMJE April 17, 2014
First Posted Date  ICMJE April 22, 2014
Results First Submitted Date  ICMJE February 10, 2017
Results First Posted Date  ICMJE June 14, 2017
Last Update Posted Date February 13, 2018
Study Start Date  ICMJE March 2014
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 12, 2017)
Overall Survival (OS) [ Time Frame: Baseline until death due to any cause; up to 16 months or data cut-off 11 FEB 2016. ]
Overall survival is defined as the time from randomization to death due to any cause. Participants without death observed at the time of the analysis will be censored at last date known to be alive. The median overall survival time was estimated using the Kaplan-Meier method. Overall survival was compared between treatment groups using log-rank test.
Original Primary Outcome Measures  ICMJE
 (submitted: April 17, 2014)
  • 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.] ]
Change History Complete list of historical versions of study NCT02119676 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2017)
  • Progression Free Survival (PFS) [ Time Frame: Baseline through disease progression, or death due to any cause if sooner; up to 16 months or data cut-off 11 FEB 2016. ]
    Progressive Disease (PD) is defined using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at least a 20% increase in the sum of the Longest Diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, unequivocal progression of non-target lesions, or the appearance of new lesions.
  • Overall Response Rate (ORR) [ Time Frame: Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016. ]
    Response defined per Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR)=disappearance of all target and non-target lesions without new lesion; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions, non-target lesion not progressed, and no new lesion; Progressive Disease=20% increase in sum of longest diameter of target lesions, or non-target lesion progression, or identification of new lesion; Stable Disease=small changes that do not meet above criteria. ORR was defined as the proportion of participants who achieved a best response of either CR or PR. ORR=number of participants with CR or PR/number of participants randomized.
  • Duration of Response [ Time Frame: Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016. ]
    Duration of response is defined as the time from response (CR/PR) until the earliest date of disease progression determined by investigator assessment of objective radiographic disease assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause.
  • Percentage of Participants Achieving Disease Control [ Time Frame: Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016. ]
    Disease control as measured by the percentage of participants whose best response was complete response (CR), partial response (PR), or stable disease (SD) per RECIST v.1.1.
  • Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline through approximately 30 days post treatment discontinuation;up to 16 months or data cut-off 27JAN 2016 for Substudy 1 and up to the data cut-off of 11FEB2016 for Substudy 2. ]
    TEAEs were defined as any adverse event (AE) during the study that began or worsened on or after the date of first dose of investigational product.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2014)
  • Progression Free Survival (PFS) [ Time Frame: Randomization through disease progression, or death due to any cause if sooner. Approximately 28 months. ]
    PFS is defined as the time from randomization until the earliest date of disease progression determined by investigator assessment of objective radiographic disease assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, if sooner
  • Objective Response Rate [ Time Frame: Baseline through end of study. Approximately 28 months. ]
    Objective response rate determined by radiographic disease assessments per RECIST v1.1, by investigator assessment
  • Duration of Response [ Time Frame: Baseline through end of study. 28 months. ]
    Duration of response determined by radiographic disease assessment per RECIST v1.1, by investigator assessment
  • 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. ]
    Disease control as measured by the percentage of subjects whose best response was not progressive disease (PD) (ie, complete response (CR), partial response (PR), or stable disease (SD) per RECIST v.1.1). Stable disease will be included if it occurs at least 6 weeks after randomization
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Ruxolitinib in Colorectal Cancer Patients
Official Title  ICMJE A Randomized, Double-Blind Study of Ruxolitinib or Placebo in Combination With Regorafenib in Subjects With Relapsed or Refractory Metastatic Colorectal Cancer
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE CRC (Colorectal Cancer)
Intervention  ICMJE
  • Drug: Ruxolitinib

    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.)

    Other Names:
    • Jakafi ®
    • Jakavi ®
  • Drug: Regorafenib
    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.)
    Other Name: Stivarga ®
  • Drug: Placebo
    5 mg matching placebo tablets to be administered by mouth
Study Arms  ICMJE
  • Experimental: Ruxolitinib plus regorafenib
    Interventions:
    • Drug: Ruxolitinib
    • Drug: Regorafenib
  • Active Comparator: Placebo plus regorafenib
    Interventions:
    • Drug: Regorafenib
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 12, 2017)
396
Original Estimated Enrollment  ICMJE
 (submitted: April 17, 2014)
373
Actual Study Completion Date  ICMJE December 2016
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
  • Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class II, III, or IV congestive heart failure, and arrhythmia requiring therapy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States,   Australia,   France,   Germany,   Israel,   Korea, Democratic People's Republic of,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02119676
Other Study ID Numbers  ICMJE INCB18424-267
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Incyte Corporation
Study Sponsor  ICMJE Incyte Corporation
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Albert Assad Incyte Corporation
PRS Account Incyte Corporation
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP