Study of Ruxolitinib in Colorectal Cancer Patients

NCT02119676 | Terminated Phase 2 Results DMC

• 1 other identifier: INCB18424-267
• Study Type: interventional
• Target: 396
• Locations: 8 countries
• Sites: 86

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.

Conditions

CRC (Colorectal Cancer)

Keywords

Metastatic Colorectal Cancer; Colon Cancer; Ruxolitinib; adenocarcinoma; regorafenib; Jakavi ®; Jakafi ®; Stivarga ®

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  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.

  Baseline until death due to any cause; up to 16 months or data cut-off 11 FEB 2016.

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  Baseline through disease progression, or death due to any cause if sooner; up to 16 months or data cut-off 11 FEB 2016.

• Overall Response Rate (ORR)

  Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016.

• Duration of Response

  Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016.

• Percentage of Participants Achieving Disease Control

  Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016.

• Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

  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.

Study Arms (2)

Ruxolitinib plus regorafenib

EXPERIMENTAL

Drug: Ruxolitinib; Drug: Regorafenib

Placebo plus regorafenib

ACTIVE COMPARATOR

Drug: Regorafenib; Drug: Placebo

Interventions

Ruxolitinib 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.)

Also known as: Jakafi ®, Jakavi ®

Ruxolitinib plus regorafenib

Regorafenib 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.)

Also known as: Stivarga ®

Placebo plus regorafenib; Ruxolitinib plus regorafenib

Placebo DRUG

5 mg matching placebo tablets to be administered by mouth

Placebo plus regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (86)

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Chandler, Arizona, United States

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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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MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Adenocarcinoma

Interventions

ruxolitinib; regorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Limitations and Caveats

Substudy 1 was terminated for futility at interim analysis and Substudy 2 was terminated per sponsor decision.

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

855 463-3463

Study Officials

• Albert Assad

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2014
• First Posted: April 22, 2014
• Study Start: March 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: December 1, 2016
• Last Updated: February 13, 2018
• Results First Posted: June 14, 2017

Record last verified: 2018-01

Locations

IL (5); ES (5); US (57); FR (6); AU (5); KR (1); GB (4); DE (3)