A Study of Ruxolitinib in Combination With Capecitabine in Subjects With Advanced or Metastatic HER2-negative Breast Cancer

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Ruxolitinib
* Drug: Capecitabine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A - Capecitabine and ruxolitinib<br> | Drug: Ruxolitinib<br>* 5 mg tablets to be administered by mouth Ruxolitinib 15 mg BID (starting dose)<br>* Other names: Jakavi ®;Drug: Capecitabine<br>* 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<br>|
| Active Comparator: Treatment B - Capecitabine and placebo<br> | Drug: Capecitabine<br>* 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<br>Drug: Placebo<br>* 5 mg matching placebo tablets to be administered by mouth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Randomization until death due to any cause up to 19 months or the data cutoff 08FEB2016. | 
| 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. | Randomization until death due to any cause up to 19 months or the data cutoff 08FEB2016. | 
| 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. | Randomization until death due to any cause at month 3, 6, 9, 12 and 15 or the data cutoff 08FEB2016. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Randomization to disease progression, or death due to any cause if sooner up to 19 months or the data cutoff 08FEB2016. | 
| 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. | Randomization through end of study up to 19 months or the data cutoff 08FEB2016. | 
| 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. | Randomization through end of study up to 19 months or the data cutoff 08FEB2016. | 
| 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. | Randomization through end of study up to 19 months or the data cutoff 08FEB2016. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer