Study of Ruxolitinib in Colorectal Cancer Patients

NCT ID: NCT02119676

Last Updated: 2018-02-13

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

396 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-31

Study Completion Date

2016-12-31

Brief Summary

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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

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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.

Conditions

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CRC (Colorectal Cancer)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Ruxolitinib plus regorafenib

Group Type EXPERIMENTAL

Ruxolitinib

Intervention Type DRUG

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.)

Regorafenib

Intervention Type DRUG

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 plus regorafenib

Group Type ACTIVE_COMPARATOR

Regorafenib

Intervention Type DRUG

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

Intervention Type DRUG

5 mg matching placebo tablets to be administered by mouth

Interventions

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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.)

Intervention Type 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.)

Intervention Type DRUG

Placebo

5 mg matching placebo tablets to be administered by mouth

Intervention Type DRUG

Other Intervention Names

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Jakafi ® Jakavi ® Stivarga ®

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Albert Assad

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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Chandler, Arizona, United States

Site Status

Gilbert, Arizona, United States

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Mesa, Arizona, United States

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Scottsdale, Arizona, United States

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Los Angeles, California, United States

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Pasadena, California, United States

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Santa Barbara, California, United States

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Aurora, Colorado, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Altamonte Springs, Florida, United States

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Miami, Florida, United States

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Ocala, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Niles, Illinois, United States

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Lafayette, Indiana, United States

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Ames, Iowa, United States

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New Orleans, Louisiana, United States

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Baltimore, Maryland, United States

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Jefferson City, Missouri, United States

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St Louis, Missouri, United States

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Lincoln, Nebraska, United States

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Omaha, Nebraska, United States

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Henderson, Nevada, United States

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Las Vegas, Nevada, United States

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Albany, New York, United States

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Binghamton, New York, United States

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Hudson, New York, United States

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Johnson City, New York, United States

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New York, New York, United States

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The Bronx, New York, United States

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Canton, Ohio, United States

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Cincinnati, Ohio, United States

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Portland, Oregon, United States

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Charleston, South Carolina, United States

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Easley, South Carolina, United States

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Greenville, South Carolina, United States

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Greer, South Carolina, United States

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Sumter, South Carolina, United States

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Chattanooga, Tennessee, United States

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Nashville, Tennessee, United States

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Arlington, Texas, United States

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El Paso, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Paris, Texas, United States

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Plano, Texas, United States

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Tyler, Texas, United States

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American Fork, Utah, United States

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Bountiful, Utah, United States

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Murray, Utah, United States

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Provo, Utah, United States

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Salt Lake City, Utah, United States

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West Jordan, Utah, United States

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Roanoke, Virginia, United States

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Vancouver, Washington, United States

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Bentleigh East, , Australia

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Herston, , Australia

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Kurralta Park, , Australia

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New Lambton Heights, , Australia

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Randwick, , Australia

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Avignon, , France

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Besançon, , France

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Le Mans, , France

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Lille, , France

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Marseille, , France

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Paris, , France

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Augsburg, , Germany

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Halle, , Germany

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Hamburg, , Germany

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Beersheba, , Israel

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Haifa, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Soeul, , South Korea

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Oviedo, Principality of Asturias, Spain

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Barcelona, , Spain

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Madrid, , Spain

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Seville, , Spain

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Valencia, , Spain

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Birmingham, , United Kingdom

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Bournemouth, , United Kingdom

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London, , United Kingdom

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Sutton, , United Kingdom

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Countries

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United States Australia France Germany Israel South Korea Spain United Kingdom

Other Identifiers

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INCB18424-267

Identifier Type: -

Identifier Source: org_study_id

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