CRC (Colorectal Cancer)Phase 2NCT02119676
Study of Ruxolitinib in Colorectal Cancer Patients
A Phase 2 study testing Ruxolitinib and Regorafenib in people with CRC (Colorectal Cancer), run by Incyte Corporation at 86 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CRC (Colorectal Cancer)
- What is being tested?
- Ruxolitinib and Regorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 396 participants
- Where
- 86 sitesin 8 countries
- Study dates
- Mar 2014to Dec 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
86 sites in 8 countries.
86 sites in 8 countries
United States57 sites
Study site
Albany, New York
Study site
Altamonte Springs, Florida
Study site
American Fork, Utah
Study site
Ames, Iowa
Study site
Arlington, Texas
Study site
Aurora, Colorado
Study site
Baltimore, Maryland
Study site
Binghamton, New York
Study site
Bountiful, Utah
Study site
Canton, Ohio
Study site
Chandler, Arizona
Study site
Charleston, South Carolina
Study site
Chattanooga, Tennessee
Study site
Cincinnati, Ohio
Study site
Colorado Springs, Colorado
Study site
Denver, Colorado
Study site
Easley, South Carolina
Study site
El Paso, Texas
Study site
Fort Worth, Texas
Study site
Gilbert, Arizona
Study site
Greenville, South Carolina
Study site
Greer, South Carolina
Study site
Henderson, Nevada
Study site
Houston, Texas
Study site
Hudson, New York
Study site
Jefferson City, Missouri
Study site
Johnson City, New York
Study site
Lafayette, Indiana
Study site
Las Vegas, Nevada
Study site
Lincoln, Nebraska
Study site
Los Angeles, California
Study site
Mesa, Arizona
Study site
Miami, Florida
Study site
Murray, Utah
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Nashville, Tennessee
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New Orleans, Louisiana
Study site
New York, New York
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Niles, Illinois
Study site
Ocala, Florida
Study site
Omaha, Nebraska
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Orlando, Florida
Study site
Paris, Texas
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Pasadena, California
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Plano, Texas
Study site
Portland, Oregon
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Provo, Utah
Study site
Roanoke, Virginia
Study site
Salt Lake City, Utah
Study site
Santa Barbara, California
Study site
Scottsdale, Arizona
Study site
St Louis, Missouri
Study site
Sumter, South Carolina
Study site
Tampa, Florida
Study site
The Bronx, New York
Study site
Tyler, Texas
Study site
Vancouver, Washington
Study site
West Jordan, Utah
France6 sites
Study site
Avignon
Study site
Besançon
Study site
Le Mans
Study site
Lille
Study site
Marseille
Study site
Paris
Australia5 sites
Study site
Bentleigh East
Study site
Herston
Study site
Kurralta Park
Study site
New Lambton Heights
Study site
Randwick
Israel5 sites
Study site
Beersheba
Study site
Haifa
Study site
Petah Tikva
Study site
Ramat Gan
Study site
Tel Aviv
Spain5 sites
Study site
Barcelona
Study site
Madrid
Study site
Oviedo, Principality of Asturias
Study site
Seville
Study site
Valencia
United Kingdom4 sites
Study site
Birmingham
Study site
Bournemouth
Study site
London
Study site
Sutton
About this study
Official title: A Randomized, Double-Blind Study of Ruxolitinib or Placebo in Combination With Regorafenib in Subjects With Relapsed or Refractory Metastatic Colorectal Cancer
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.
Read the 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.
- Conditions
- CRC (Colorectal Cancer)
- Being tested
- Ruxolitinib, Regorafenib, Placebo
- Keywords
- Metastatic Colorectal Cancer, Colon Cancer, Ruxolitinib, adenocarcinoma, regorafenib, Jakavi ®, Jakafi ®, Stivarga ®
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
Also called Jakafi ®, Jakavi ®
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.)
RegorafenibDrug
Also called Stivarga ®
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.)
PlaceboDrug
5 mg matching placebo tablets to be administered by mouth
| Study group | Role | What they receive |
|---|---|---|
| Ruxolitinib plus regorafenib | Experimental | Not described Receives: Drug: Ruxolitinib; Drug: Regorafenib |
| Placebo plus regorafenib | Active comparator | Not described Receives: Drug: Regorafenib; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016.
Duration of Response
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.
Measured: Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016.
Percentage of Participants Achieving Disease Control
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.
Measured: 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)
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2014 (estimated)
- Study startMar 2014
- Primary completionFeb 2016
- Study completionDec 2016
Why it stopped: Substudy 1 was terminated for futility at interim analysis and Substudy 2 was terminated per sponsor decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CRC (Colorectal Cancer)Studies of the same condition, open and under way.
- More trials run by Incyte CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 396 participants (actual)
Sponsor and investigators
- Lead sponsor
- Incyte Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Albert Assad, Study director, Incyte Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02119676
- Sponsor's protocol ID
- INCB18424-267
- Status last verified
- Jan 2018
- First submitted
- 17 Apr 2014
- Last updated
- 13 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind Study of Ruxolitinib or Placebo in Combination With Regorafenib in Subjects With Relapsed or Refractory Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT02119676
- Acronym / sponsor ID
- INCB18424-267
- Conditions
- CRC (Colorectal Cancer)
- Keywords
- Metastatic Colorectal Cancer, Colon Cancer, Ruxolitinib, adenocarcinoma, regorafenib, Jakavi ®, Jakafi ®, Stivarga ®
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Substudy 1 was terminated for futility at interim analysis and Substudy 2 was terminated per sponsor decision.
- Enrolment
- 396 participants (actual)
- Lead sponsor
- Incyte CorporationIndustry (pharma, biotech, devices)
- Study start
- Mar 2014
- Primary completion
- Feb 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 22 Apr 2014 (estimated)
- Results
- Posted 14 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ruxolitinib plus regorafenib | Experimental | Drug: Ruxolitinib, Drug: Regorafenib |
| Placebo plus regorafenib | Active comparator | Drug: Regorafenib, Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RuxolitinibAlso: Jakafi ®, Jakavi ®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.) | Drug | Ruxolitinib plus regorafenib |
| RegorafenibAlso: Stivarga ®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.) | Drug | Placebo plus regorafenib, Ruxolitinib plus regorafenib |
| Placebo5 mg matching placebo tablets to be administered by mouth | Drug | Placebo plus regorafenib |
Primary outcome
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.
5 secondary outcomes
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.
Overall Response Rate (ORR)
Time frame: Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016.
Duration of Response
Time frame: Baseline through end of study; up to 16 months or data cut-off 11 FEB 2016.
Percentage of Participants Achieving Disease Control
Time frame: 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)
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Albert Assad study director
Incyte Corporation
86 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ruxolitinib and Regorafenib in people with CRC (Colorectal Cancer), run by Incyte Corporation at 86 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 86 sites in United States, France, Australia, Israel, Spain and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: Baseline until death due to any cause; up to 16 months or data cut-off 11 FEB 2016.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2018.