Breast Cancer
Conditions
Keywords
Breast Cancer
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.
Interventions
DRUGRuxolitinib
5 mg tablets to be administered by mouth Ruxolitinib 15 mg BID (starting dose)
DRUGCapecitabine
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
DRUGPlacebo
5 mg matching placebo tablets to be administered by mouth
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. modified Glasgow prognostic score (mGPS) of 1: CRP \> 10 mg/L and albumin ≥ 35 g/L 2. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Randomization until death due to any cause up to 19 months or the data cutoff 08FEB2016. | 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 | Randomization until death due to any cause up to 19 months or the data cutoff 08FEB2016. | 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 | Randomization until death due to any cause at month 3, 6, 9, 12 and 15 or the data cutoff 08FEB2016. | 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
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Randomization to disease progression, or death due to any cause if sooner up to 19 months or the data cutoff 08FEB2016. | 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 Clinical Benefit Rate | Randomization through end of study up to 19 months or the data cutoff 08FEB2016. | 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. |
| Percentage of Participants Achieving Objective Response Rate | Randomization through end of study up to 19 months or the data cutoff 08FEB2016. | 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) | Randomization through end of study up to 19 months or the data cutoff 08FEB2016. | 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. |
Countries
France, Italy, Portugal, Spain, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 72 study centers (65 in the United States and 7 in the European Union \[3 in the United Kingdom, 3 in Spain, and 1 in Portugal\]).
Participants by arm
| Arm | Count |
|---|---|
| Treatment A - Capecitabine and Ruxolitinib Capecitabine given as 1000 mg/m\^2 twice a day (BID) on day 1 to day 14 of each 21-day cycle with the addition of Ruxolitinib 15 mg (three 5 mg tablets) BID to be administered by mouth on day 1 to day 21 of each 21-day cycle | 76 |
| Treatment B - Capecitabine and Placebo Capecitabine given as 1000 mg/m\^2 twice a day (BID) on day 1 to day 14 of each 21-day cycle with the addition of 15 mg (three 5 mg tablets) matching placebo BID to be administered by mouth on day 1 to day 21 of each 21-day cycle | 73 |
| Total | 149 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 9 |
| Overall Study | Death | 5 | 1 |
| Overall Study | Disease progression | 41 | 45 |
| Overall Study | Noncompliance with study treatment | 0 | 2 |
| Overall Study | Other unspecified | 5 | 4 |
| Overall Study | Participant decision | 4 | 4 |
| Overall Study | Physician Decision | 2 | 3 |
Baseline characteristics
| Characteristic | Treatment A - Capecitabine and Ruxolitinib | Treatment B - Capecitabine and Placebo | Total |
|---|---|---|---|
| Age, Continuous | 54.3 years STANDARD_DEVIATION 11 | 55.0 years STANDARD_DEVIATION 12.75 | 54.6 years STANDARD_DEVIATION 11.85 |
| Sex: Female, Male Female | 76 Participants | 73 Participants | 149 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 69 / 71 | 69 / 71 |
| serious Total, serious adverse events | 28 / 71 | 29 / 71 |
Outcome results
Primary
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.
Time frame: Randomization until death due to any cause up to 19 months or the data cutoff 08FEB2016.
Population: The Intent-to-Treat (ITT) population consisted of all participants randomized to the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A - Capecitabine and Ruxolitinib | Median Survival | 11.2 months |
| Treatment B - Capecitabine and Placebo | Median Survival | 10.9 months |
Primary
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.
Time frame: Randomization until death due to any cause up to 19 months or the data cutoff 08FEB2016.
Population: The Intent-to-Treat (ITT) population consisted of all participants randomized to the study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A - Capecitabine and Ruxolitinib | Overall Survival (OS) | Death events | 39 Participants |
| Treatment A - Capecitabine and Ruxolitinib | Overall Survival (OS) | Censored events | 37 Participants |
| Treatment B - Capecitabine and Placebo | Overall Survival (OS) | Death events | 38 Participants |
| Treatment B - Capecitabine and Placebo | Overall Survival (OS) | Censored events | 35 Participants |
p-value: 0.76280% CI: [0.694, 1.252]Log Rank
Primary
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.
Time frame: Randomization until death due to any cause at month 3, 6, 9, 12 and 15 or the data cutoff 08FEB2016.
Population: The Intent-to-Treat (ITT) population consisted of all participants randomized to the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A - Capecitabine and Ruxolitinib | Percentage of Participants Achieving Overall Survival | Month 6 Survival Rate | 0.674 percentage of participants |
| Treatment A - Capecitabine and Ruxolitinib | Percentage of Participants Achieving Overall Survival | Month 12 Survival Rate | 0.435 percentage of participants |
| Treatment A - Capecitabine and Ruxolitinib | Percentage of Participants Achieving Overall Survival | Month 9 Survival Rate | 0.537 percentage of participants |
| Treatment A - Capecitabine and Ruxolitinib | Percentage of Participants Achieving Overall Survival | Month 15 Survival Rate | 0.319 percentage of participants |
| Treatment A - Capecitabine and Ruxolitinib | Percentage of Participants Achieving Overall Survival | Month 3 Survival Rate | 0.855 percentage of participants |
| Treatment B - Capecitabine and Placebo | Percentage of Participants Achieving Overall Survival | Month 15 Survival Rate | 0.294 percentage of participants |
| Treatment B - Capecitabine and Placebo | Percentage of Participants Achieving Overall Survival | Month 3 Survival Rate | 0.750 percentage of participants |
| Treatment B - Capecitabine and Placebo | Percentage of Participants Achieving Overall Survival | Month 6 Survival Rate | 0.635 percentage of participants |
| Treatment B - Capecitabine and Placebo | Percentage of Participants Achieving Overall Survival | Month 9 Survival Rate | 0.546 percentage of participants |
| Treatment B - Capecitabine and Placebo | Percentage of Participants Achieving Overall Survival | Month 12 Survival Rate | 0.427 percentage of participants |
Secondary
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.
Time frame: Randomization through end of study up to 19 months or the data cutoff 08FEB2016.
Population: The Intent-to-Treat (ITT) population consisted of all participants randomized to the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A - Capecitabine and Ruxolitinib | Duration of Response (DOR) | 4.2 months |
| Treatment B - Capecitabine and Placebo | Duration of Response (DOR) | 4.4 months |
Secondary
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.
Time frame: Randomization through end of study up to 19 months or the data cutoff 08FEB2016.
Population: The Intent-to-Treat (ITT) population consisted of all participants randomized to the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A - Capecitabine and Ruxolitinib | Percentage of Participants Achieving Clinical Benefit Rate | 13.2 percentage of participants |
| Treatment B - Capecitabine and Placebo | Percentage of Participants Achieving Clinical Benefit Rate | 6.8 percentage of participants |
Secondary
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.
Time frame: Randomization through end of study up to 19 months or the data cutoff 08FEB2016.
Population: The Intent-to-Treat (ITT) population consisted of all participants randomized to the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A - Capecitabine and Ruxolitinib | Percentage of Participants Achieving Objective Response Rate | Complete Response rate | 0.0 percentage of participants |
| Treatment A - Capecitabine and Ruxolitinib | Percentage of Participants Achieving Objective Response Rate | Partial Response rate | 28.9 percentage of participants |
| Treatment B - Capecitabine and Placebo | Percentage of Participants Achieving Objective Response Rate | Complete Response rate | 0.0 percentage of participants |
| Treatment B - Capecitabine and Placebo | Percentage of Participants Achieving Objective Response Rate | Partial Response rate | 13.7 percentage of participants |
Secondary
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.
Time frame: Randomization to disease progression, or death due to any cause if sooner up to 19 months or the data cutoff 08FEB2016.
Population: The Intent-to-Treat (ITT) population consisted of all participants randomized to the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A - Capecitabine and Ruxolitinib | Progression-free Survival (PFS) | 4.5 months |
| Treatment B - Capecitabine and Placebo | Progression-free Survival (PFS) | 2.5 months |