Clinical trial NCT02119676: Study of Ruxolitinib in Colorectal Cancer Patients
Official title: A Randomized, Double-Blind Study of Ruxolitinib or Placebo in Combination With Regorafenib in Subjects With Relapsed or Refractory Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: CRC (Colorectal Cancer)
Keywords: Metastatic Colorectal Cancer
Colon Cancer
Ruxolitinib
adenocarcinoma
regorafenib
Jakavi ®
Jakafi ®
Stivarga ®
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2014-04-22
Enrollment: 396
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Baseline until death due to any cause; up to 16 months or data cut-off 11 FEB 2016.
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Baseline through disease progression, or death due to any cause if sooner; up to 16 months or data cut-off 11 FEB 2016.
measure: Overall Response Rate (ORR)
timeFrame: Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016.
measure: Duration of Response
timeFrame: Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016.
measure: Percentage of Participants Achieving Disease Control
timeFrame: Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016.
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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.
Other outcomes:
Locations:
city: Chandler
country: United States
state: Arizona
city: Gilbert
country: United States
state: Arizona
city: Mesa
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Pasadena
country: United States
state: California
city: Santa Barbara
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Colorado Springs
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Altamonte Springs
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Niles
country: United States
state: Illinois
city: Lafayette
country: United States
state: Indiana
city: Ames
country: United States
state: Iowa
city: New Orleans
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Jefferson City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Lincoln
country: United States
state: Nebraska
city: Omaha
country: United States
state: Nebraska
city: Henderson
country: United States
state: Nevada
city: Las Vegas
country: United States
state: Nevada
city: Albany
country: United States
state: New York
city: Binghamton
country: United States
state: New York
city: Bronx
country: United States
state: New York
city: Hudson
country: United States
state: New York
city: Johnson City
country: United States
state: New York
city: New York
country: United States
state: New York
city: Canton
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Charleston
country: United States
state: South Carolina
city: Easley
country: United States
state: South Carolina
city: Greenville
country: United States
state: South Carolina
city: Greer
country: United States
state: South Carolina
city: Sumter
country: United States
state: South Carolina
city: Chattanooga
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: El Paso
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Paris
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: American Fork
country: United States
state: Utah
city: Bountiful
country: United States
state: Utah
city: Murray
country: United States
state: Utah
city: Provo
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: West Jordan
country: United States
state: Utah
city: Roanoke
country: United States
state: Virginia
city: Vancouver
country: United States
state: Washington
city: Bentleigh East
country: Australia
city: Herston
country: Australia
city: Kurralta Park
country: Australia
city: New Lambton Heights
country: Australia
city: Randwick
country: Australia
city: Avignon Cedex 09
country: France
city: Besançon
country: France
city: Le Mans
country: France
city: Lille
country: France
city: Marseille Cedex 05
country: France
city: Paris
country: France
city: Augsburg
country: Germany
city: Halle
country: Germany
city: Hamburg
country: Germany
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Petah Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Tel Aviv
country: Israel
city: Soeul
country: Korea, Republic of
city: Oviedo
country: Spain
state: Asturias
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Birmingham
country: United Kingdom
city: Bournemouth
country: United Kingdom
city: London
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
affiliation: Incyte Corporation
name: Albert Assad
role: STUDY_DIRECTOR
References: