Back to resultsA Study of Ruxolitinib in Combination With Capecitabine in Subjects With Advanced or Metastatic HER2-negative Breast Cancer
Primary Purpose
Breast Cancer
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ruxolitinib
Capecitabine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed HER2-negative adenocarcinoma of the breast
- Locally advanced (Stage 3B) or metastatic (Stage 4) disease
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Received up to 2 prior chemotherapy regimens (not including neoadjuvant/adjuvant therapy) for advanced or metastatic disease
- Participants with hormone-receptor positive tumors must have failed available lines of hormonal therapy unless hormone therapy was not tolerated or not clinically appropriate
- ≥ 2 weeks elapsed from the completion of previous treatment regimen and must have recovered or be at a new stable baseline from any related toxicities
- Radiographically measurable or evaluable disease
An mGPS of 1 or 2 as defined below:
Criteria:
- modified Glasgow prognostic score (mGPS) of 1: CRP > 10 mg/L and albumin ≥ 35 g/L
- mGPS of 2: C-reactive protein (CRP) > 10 mg/L and albumin < 35 g/L
Exclusion Criteria:
- Received prior treatment with capecitabine or fluoropyrimidine for advanced or metastatic disease
- Received more than 2 prior regimens for advanced or metastatic disease (not including hormonal therapy in the metastatic setting or neoadjuvant or adjuvant therapies)
- Unknown hormone-receptor status
- Ongoing radiation therapy or radiation therapy administered within 2 weeks of enrollment
- Concurrent anticancer therapy
- Inadequate renal, hepatic or bone marrow function
- Another current or previous malignancy within 2 years of study entry unless approved by the sponsor
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Treatment A - Capecitabine and ruxolitinib
Treatment B - Capecitabine and placebo
Arm Description
Outcomes
Primary Outcome Measures
Overall Survival (OS)
Overall survival is reported here by the number of days from randomization to death until the data cutoff for the final analysis. The hazard ratio (80% CI) for ruxolitinib versus placebo was estimated using a Cox regression model stratified by hormone-receptor status.
Median Survival
Survival was assessed by the time to death or censoring up until 08Feb2016. Participants with no observed death were treated as right-censored at their last date known to be alive. The survival time was analyzed using the Kaplan-Meier method.
Percentage of Participants Achieving Overall Survival
Overall survival was assessed by the time to death or censoring up until 08Feb2016. Participants with no observed death were treated as right-censored at their last date known to be alive. The survival time was analyzed using the Kaplan-Meier method.
Secondary Outcome Measures
Progression-free Survival (PFS)
Progression-free survival was defined as the time from the randomization date to the earliest date of disease progression, as measured by investigator assessment of objective radiographic disease assessments per RECIST (v1.1), or death from any cause if earlier. Progression-free survival time distribution and median survival for each treatment group were analyzed using the Kaplan-Meier method.
Percentage of Participants Achieving Objective Response Rate
Objective response rate determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment and was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) by Response Evaluation Criteria in Solid Tumours (RECIST) at any post baseline visit. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI) : Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions with no worsening of non-target lesions and no new lesions; Overall Response (OR) = CR + PR.
Duration of Response (DOR)
The DOR was defined as the difference (in number of months) between the end of response and the start of response for participants who had at least 1 response measurement. The start of a response was the first visit where the participant achieved a partial response or better based on RECIST (v1.1) criteria. The end of response was the earlier of death or progressive disease based on RECIST (v1.1) criteria. The date of progressive disease was the date on which progression was first recorded. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI) : Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions with no worsening of non-target lesions and no new lesions; Overall Response (OR) = CR + PR.
Percentage of Participants Achieving Clinical Benefit Rate
Clinical benefit rate was defined as a complete response, partial response, or stable disease, determined by investigator assessment of objective radiographic disease assessments per RECIST (v1.1) that lasted for ≥ 6 months. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI) : Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions with no worsening of non-target lesions and no new lesions; Overall Response (OR) = CR + PR.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02120417
Brief Title
A Study of Ruxolitinib in Combination With Capecitabine in Subjects With Advanced or Metastatic HER2-negative Breast Cancer
Official Title
A Randomized, Double-Blind, Phase 2 Study of Ruxolitinib or Placebo in Combination With Capecitabine in Subjects With Advanced or Metastatic HER2-Negative Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated as other related studies of ruxolitinib did not provide sufficient efficacy to warrant continuation.
Study Start Date
May 2014 (Actual)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
January 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This was a randomized, double-blind, placebo-controlled phase 2 clinical trial comparing the overall survival of women with advanced or metastatic HER2-negative breast cancer who received treatment with capecitabine in combination with ruxolitinib versus those who received treatment with capecitabine alone.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
149 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment A - Capecitabine and ruxolitinib
Arm Type
Experimental
Arm Title
Treatment B - Capecitabine and placebo
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
Jakafi ®, Jakavi ®
Intervention Description
5 mg tablets to be administered by mouth
Ruxolitinib 15 mg BID (starting dose)
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Capecitabine 2000 mg/m^2 daily given as 1000 mg/m^2 twice a day (BID) (starting dose) Day 1-14 of each 21 day cycle
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
5 mg matching placebo tablets to be administered by mouth
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Overall survival is reported here by the number of days from randomization to death until the data cutoff for the final analysis. The hazard ratio (80% CI) for ruxolitinib versus placebo was estimated using a Cox regression model stratified by hormone-receptor status.
Time Frame
Randomization until death due to any cause up to 19 months or the data cutoff 08FEB2016.
Title
Median Survival
Description
Survival was assessed by the time to death or censoring up until 08Feb2016. Participants with no observed death were treated as right-censored at their last date known to be alive. The survival time was analyzed using the Kaplan-Meier method.
Time Frame
Randomization until death due to any cause up to 19 months or the data cutoff 08FEB2016.
Title
Percentage of Participants Achieving Overall Survival
Description
Overall survival was assessed by the time to death or censoring up until 08Feb2016. Participants with no observed death were treated as right-censored at their last date known to be alive. The survival time was analyzed using the Kaplan-Meier method.
Time Frame
Randomization until death due to any cause at month 3, 6, 9, 12 and 15 or the data cutoff 08FEB2016.
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
Progression-free survival was defined as the time from the randomization date to the earliest date of disease progression, as measured by investigator assessment of objective radiographic disease assessments per RECIST (v1.1), or death from any cause if earlier. Progression-free survival time distribution and median survival for each treatment group were analyzed using the Kaplan-Meier method.
Time Frame
Randomization to disease progression, or death due to any cause if sooner up to 19 months or the data cutoff 08FEB2016.
Title
Percentage of Participants Achieving Objective Response Rate
Description
Objective response rate determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment and was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) by Response Evaluation Criteria in Solid Tumours (RECIST) at any post baseline visit. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI) : Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions with no worsening of non-target lesions and no new lesions; Overall Response (OR) = CR + PR.
Time Frame
Randomization through end of study up to 19 months or the data cutoff 08FEB2016.
Title
Duration of Response (DOR)
Description
The DOR was defined as the difference (in number of months) between the end of response and the start of response for participants who had at least 1 response measurement. The start of a response was the first visit where the participant achieved a partial response or better based on RECIST (v1.1) criteria. The end of response was the earlier of death or progressive disease based on RECIST (v1.1) criteria. The date of progressive disease was the date on which progression was first recorded. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI) : Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions with no worsening of non-target lesions and no new lesions; Overall Response (OR) = CR + PR.
Time Frame
Randomization through end of study up to 19 months or the data cutoff 08FEB2016.
Title
Percentage of Participants Achieving Clinical Benefit Rate
Description
Clinical benefit rate was defined as a complete response, partial response, or stable disease, determined by investigator assessment of objective radiographic disease assessments per RECIST (v1.1) that lasted for ≥ 6 months. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI) : Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions with no worsening of non-target lesions and no new lesions; Overall Response (OR) = CR + PR.
Time Frame
Randomization through end of study up to 19 months or the data cutoff 08FEB2016.
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed HER2-negative adenocarcinoma of the breast
Locally advanced (Stage 3B) or metastatic (Stage 4) disease
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
Received up to 2 prior chemotherapy regimens (not including neoadjuvant/adjuvant therapy) for advanced or metastatic disease
Participants with hormone-receptor positive tumors must have failed available lines of hormonal therapy unless hormone therapy was not tolerated or not clinically appropriate
≥ 2 weeks elapsed from the completion of previous treatment regimen and must have recovered or be at a new stable baseline from any related toxicities
Radiographically measurable or evaluable disease
An mGPS of 1 or 2 as defined below:
Criteria:
modified Glasgow prognostic score (mGPS) of 1: CRP > 10 mg/L and albumin ≥ 35 g/L
mGPS of 2: C-reactive protein (CRP) > 10 mg/L and albumin < 35 g/L
Exclusion Criteria:
Received prior treatment with capecitabine or fluoropyrimidine for advanced or metastatic disease
Received more than 2 prior regimens for advanced or metastatic disease (not including hormonal therapy in the metastatic setting or neoadjuvant or adjuvant therapies)
Unknown hormone-receptor status
Ongoing radiation therapy or radiation therapy administered within 2 weeks of enrollment
Concurrent anticancer therapy
Inadequate renal, hepatic or bone marrow function
Another current or previous malignancy within 2 years of study entry unless approved by the sponsor
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerard Kennealey, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
City
Birmingham
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Alabama
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United States
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Chandler
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Sedona
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La Jolla
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Oxnard
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Santa Monica
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Hialeah
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Miami
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Plantation
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Saint Petersburg
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Tampa
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Atlanta
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Marietta
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Savannah
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Chicago
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Ames
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Wichita
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Louisville
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Detroit
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Omaha
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Camden
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Hackensack
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Bronx
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New York
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Cleveland
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Columbus
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Middletown
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Portland
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Greenville
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Chattanooga
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Germantown
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Nashville
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Arlington
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Bedford
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Dallas
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El Paso
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Fort Worth
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Houston
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McAllen
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Plano
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Tyler
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Ogden
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Salt Lake City
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Fairfax
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Norfolk
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Richmond
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Salem
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Virginia
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Seattle
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Green Bay
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Wisconsin
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Milwaukee
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Wisconsin
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La Roche Sur Yon
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France
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Paris Cedex 10
Country
France
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Paris
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France
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Alba
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Italy
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Fano
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Italy
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Foggia
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Italy
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Lecco
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Italy
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Milano
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Italy
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Naples
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Italy
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Pontedera
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Italy
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Roma
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Italy
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Saronno
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Italy
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Lisbon
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Portugal
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A Coruña
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Spain
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Barcelona
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Spain
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Jaén
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Spain
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Lleida
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Spain
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Madrid
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Spain
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Cardiff
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Glasgow
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Kingston Upon Thames
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London
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Nottingham
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Sutton
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United Kingdom
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Taunton
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United Kingdom
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Truro
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United Kingdom
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Yeovil
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United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of Ruxolitinib in Combination With Capecitabine in Subjects With Advanced or Metastatic HER2-negative Breast Cancer
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