Metastatic or advanced HER-2 negative breast cancer patients who have already received treatment with anthracyclines and paclitaxel. MedDRA version: 17.0 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
Conditions
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Women aged 18 years or older. 2.Histologically or cytologically confirmed HER2-negative adenocarcinoma of the breast, including ER+, PR+, and TNBC. 3.Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent. 4.Modified GPS of 1 or 2 as defined below: a. mGPS of 1: CRP > 10 mg/L and albumin = 35 g/L b. mGPS of 2: CRP > 10 mg/L and albumin =65 years) yes F.1.3.1 Number of subjects for this age range 98
Exclusion criteria
Exclusion criteria: 1.Received prior treatment with capecitabine or fluoropyrimidine for advanced or metastatic disease. 2.Received more than 2 prior regimens for advanced or metastatic disease (not including hormonal therapy in the metastatic setting, or neoadjuvant and adjuvant therapies). 3.Unknown hormone-receptor status (ER and PR). 6.Untreated brain metastases, or brain metastases that have progressed Subjects with treated and clinically stable brain metastases and off all corticosteroids for at least 4 weeks are eligible. 7.Inadequate renal, hepatic, and bone marrow function as evidenced by: a.Absolute neutrophil count 2.5 × upper limit of normal (ULN); or > 5 × ULN in the presence of liver metastases. e.Total bilirubin > 1.5 × ULN (if total bilirubin is > 1.5 × ULN then direct bilirubin must be = 1.5 × ULN). f.Creatinine clearance < 50 mL/min measured or calculated by Cockroft-Gault equation or the estimated glomerular filtration rate < 50 mL/min/1.73 m2 using the Modification of Diet in Renal Disease formula. 8.Significant concurrent, uncontrolled medical condition, including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral or psychiatric disease. 9.Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment. 10.Clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy. 11.Ongoing radiation therapy or radiation therapy administered within 2 weeks of enrollment. 12.Concurrent anticancer therapy 13.Subjects who participated in any other study in which receipt of an investigational study drug occurred within 28 days or 5 half-lives (whichever is longer) before first dose. For investigational agents with long half-lives, enrollment before the fifth half-life requires medical monitor approval. 14.Current or previous other malignancy within 2 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without sponsor approval. 15.Recent (= 3 months) history or ongoing partial or complete bowel obstruction. 16.Prior severe reaction to fluoropyrimidines, known dihydropyrimidine dehydrogenase deficiency, or other known hypersensitivity to active substances, including 5 FU, ruxolitinib, or any of their excipients. 17.Known history of human immunodeficiency virus infection. 18.Active hepatitis B or C infection that requires treatment. 19.Unwilling to be transfused with blood components. 20.Prior treatment with a JAK-inhibitor for any indication. 21. Pregnant or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate and compare the OS of subjects with advanced or metastatic HER2 negative breast cancer when treated with ruxolitinib in combination with capecitabine versus capecitabine alone.;Secondary Objective: To evaluate and compare the efficacy of the 2 treatment groups with respect to PFS. To evaluate and compare the efficacy of the 2 treatment groups with respect to overall tumor response and duration of response. To evaluate and compare the efficacy of the 2 treatment groups with respect to clinical benefit rate. To evaluate and compare the safety and tolerability of ruxolitinib in combination with capecitabine versus capecitabine alone. ;Primary end point(s): Overall survival as determined from the date of randomization until death due to any cause.;Timepoint(s) of evaluation of this end point: The primary endpoint is overall survival, defined as number of days from randomization to death. This analysis will be based on the ITT population, according to treatment assignment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Progression-free survival defined as the time from randomization until the earliest date of disease progression determined by investigator assessment of objective radiographic disease assessments per RECIST (v1.1), or death due to any cause, if sooner. •Objective response rate and duration of response determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment. •Clinical benefit rate defined as a complete response, partial response, or stable disease, determined by investigator assessment of objective radiographic disease assessments per RECIST (v1.1) that lasts for = 6 months. •Safety and tolerability of the treatment regimens through assessment of AEs and changes in safety assessments, including laboratory parameters. ;Timepoint(s) of evaluation of this end point: Progression-free survival will be determined from the randomization date until the earliest date of disease progression, as measured by investigator assessment of objective radiographic disease assessments per RECIST (v1.1), or death due to any cause if earlier. For the analysis of objective response, each subject will be considered a responder if his or her best overall response is a PR or better based on RECIST (v1.1). The duration of response is defined as the difference of the end of response and the start of response for subjects who have at least 1 response measurement. The start of a response will be the first visit where the subject achieves a PR or better based on RECIST (v1.1). The end of response will be the first visit after PD based on RECIST (v1.1). | — |
Countries
European Union, Italy, Portugal, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
Incyte
Outcome results
None listed