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.
Brief Title
Study of Ruxolitinib in Colorectal Cancer Patients
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
CRC (Colorectal Cancer)
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.
* 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.
Inclusion 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.
* 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.
Gender
All
Gender Based
false
Keywords
Metastatic Colorectal Cancer
Colon Cancer
Ruxolitinib
adenocarcinoma
regorafenib
Jakavi ®
Jakafi ®
Stivarga ®
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02119676
Org Class
Industry
Org Full Name
Incyte Corporation
Org Study Id
INCB18424-267
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Randomized, Double-Blind Study of Ruxolitinib or Placebo in Combination With Regorafenib in Subjects With Relapsed or Refractory Metastatic Colorectal Cancer
Primary Outcomes
Outcome Description
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.
Outcome Measure
Overall Survival (OS)
Outcome Time Frame
Baseline until death due to any cause; up to 16 months or data cut-off 11 FEB 2016.
Secondary Outcomes
Outcome Description
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.
Outcome 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.
Outcome Measure
Progression Free Survival (PFS)
Outcome Description
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.
Outcome Time Frame
Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016.
Outcome Measure
Overall Response Rate (ORR)
Outcome Description
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.
Outcome Time Frame
Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016.
Outcome Measure
Duration of Response
Outcome Description
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.
Outcome Time Frame
Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016.
Outcome Measure
Percentage of Participants Achieving Disease Control
Outcome Description
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.
Outcome 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.
Outcome Measure
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sanjay Goel
Investigator Email
sgoel@montefiore.org
Investigator Phone
718-405-8404
Categories Mesh Debug
Gastrointestinal (GI) Cancers --- COLORECTAL NEOPLASMS
Endocrine System Cancers --- ADENOCARCINOMA
Gastrointestinal (GI) Cancers --- INTESTINAL NEOPLASMS
Gastrointestinal (GI) Cancers --- GASTROINTESTINAL NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Gastrointestinal (GI) Cancers --- GASTROINTESTINAL DISEASES
Digestive System --- GASTROINTESTINAL DISEASES
Gastrointestinal (GI) Cancers --- COLONIC DISEASES
Digestive System --- COLONIC DISEASES
Gastrointestinal (GI) Cancers --- INTESTINAL DISEASES
Digestive System --- INTESTINAL DISEASES
Cancer --- CARCINOMA
Lung & Chest Cancers --- NEOPLASMS, GLANDULAR AND EPITHELIAL
MeSH Terms
COLORECTAL NEOPLASMS
COLONIC NEOPLASMS
ADENOCARCINOMA
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
RUXOLITINIB
REGORAFENIB
COUNTERFEIT DRUGS
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS