Women with recurrent or progressive locally-advanced or metastatic breast cancer
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed written informed consent according to institutional guidelines Target population 2) Invasive breast cancer based on previous biopsy with documented amplification of Her2/neu (regardless of ER/PgR status; Group A) or expression of Estrogen and/or Progesterone Receptor (Group B); see Protocol section 3.2.1 for details. 3) A paraffin-embedded tissue block from prior surgery must be available 4) Measurable, recurrent or progressive, locally-advanced or metastatic disease assessed within 28 days prior to study drug start (see Protocol section 3.2). At least one target lesion (see Protocol section 3.3.2) must be identified. 5) Prior chemotherapy including an anthracycline and a taxane, and with trastuzumab (Group A) and/or hormonal therapy (either Group) 6) One or two chemotherapy regimens in the metastatic setting 7) Recovered to Grade = 1 from toxicities of prior therapy (except alopecia) 8) Performance status (ECOG) 0 - 1 9) Adequate organ function (CTCAE v.3.0 severity grading): a) Hepatic enzymes (AST, ALT), Total bilirubin all Grade 0 – 1 b) Serum Ca2+ = Lower Limit of Normal (LLN) c) Serum K+, Mg2+, Phosphate all Grade 0 – 1 d) Creatinine Grade 0 – 2 e) Hemoglobin, Neutrophil count, Platelets, PT, PTT all Grade 0 – 1 Age and Sex 10) Females, age =18 years Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Sex and Reproductive Status 1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the study. 2) Women who are pregnant or breastfeeding 3) Women with a positive pregnancy test on enrollment or prior to study drug administration Target Disease Exceptions 4) Metastatic disease confined to bone only 5) Symptomatic CNS metastasis (see Protocol section 7.2.1) Medical History and Concurrent Diseases 6) Any anti-neoplastic therapy, including radiotherapy, or intravenous bisphosphonate within 14 days prior to study drug start (21 days for trastuzumab) 7) Other malignancy requiring radiotherapy or systemic treatment within 3 years 8) Concurrent medical condition which may increase the risk of toxicity, including: a) Pleural or pericardial effusion of any grade b) Clinically-significant coagulation or platelet function disorder (e.g. known von Willebrand’s disease) c) Infection requiring intravenous antibiotics d) Requirement for prohibited concomitant therapy (for details, see Protocol section 6.4.1) e) Ongoing or recent (=3 months) significant gastrointestinal bleeding f) Clinically-significant cardiovascular disease, including myocardial infarction or ventricular tachyarrhythmia within 6 months, prolonged QTc >450 msec. (Fridericia correction), EF <40% or major conduction abnormality (unless a cardiac pacemaker is present) g) Other medical condition which in the opinion of the Investigator might confer an unacceptable increase in risk Other Exclusion Criteria 9) Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study. 10) Inability to take oral medication for any reason 11) Inability to understand the potential risks and provide informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate, by subgroup, objective response rate (ORR) of dasatinib in women with recurrent or progressive locally-advanced or metastatic breast cancer.;Secondary Objective: 1. To estimate, by subgroup, Disease Control Rate (DCR) and proportion free of progression at week 9, 17 and 25, Progression-Free Survival (PFS) distribution, and response duration 2. To determine the safety and tolerability of dasatinib in this population 3. To obtain pharmacokinetic (PK) and pharmacodynamic data 4. To obtain exploratory tumor biomarker and pharmacogenomic data;Primary end point(s): Efficacy: Anti-tumor efficacy will be assessed by radiographic or clinical measurement. Primary analysis will be radiographically-defined ORR by RECIST criteria. Disease control rate (DCR) will be the key secondary efficacy endpoint and basis for interim analysis. Safety/tolerability: Safety and tolerability is a main secondary endpoint. Adverse events will be assessed continuously and graded according to NCI Common Terminology Criteria for Adverse Events version 3.0 (CTCAEv3) for all treated subjects. | — |
Countries
Belgium, France, Italy
Outcome results
None listed