Trial of Dasatinib Plus Ixabepilone in 2nd or 3rd Line Metastatic Breast Cancer

Inclusion Criteria

A patient must meet each of the following criteria to be considered eligible for inclusion in this study:

• Patient has the ability to understand and the willingness to sign a written informed consent including form according to institutional guidelines.
• Patient has histologically-proven breast cancer.
• Patient has locally recurrent or metastatic disease, measurable or non- measurable by RECIST criteria.
• Patient has HER2-negative disease or disease that is refractory to HER2- directed therapy.
• Patient is female or male ≥ 18 years of age.
• Patient has(ECOG)performance status of ≤ 2.
• Patient must have received at least 1 but no more than 2 prior chemotherapy regimens for locally recurrent or metastatic disease. Patients may have received neoadjuvant and/or adjuvant chemotherapy. These prior regimens can not have included ixabepilone or dasatinib. A line of chemotherapy will be defined as one or more agents used continuously or discontinuously (i.e., allowing a break or chemo holiday) without the addition of a new agent. Hormonal therapy will not be considered a line of therapy.
• Prior chemotherapy must have been completed at least 3 weeks prior to study treatment start (6 weeks for nitrosoureas and mitomycin), and the patient must have recovered from all associated toxicities (except for alopecia and neuropathy grade 1 according to CTCAE, v3.0 classification).
• Radiation therapy, immunotherapy, biologic therapy, and hormonal/endocrine therapy must have been completed at least 2 weeks prior to study treatment start. Any major surgery must have been completed at least 4 weeks prior to study treatment start.
• Patient has adequate organ, metabolic and bone marrow function as follows:
• Total bilirubin ≤ 1.0 × institutional ULN
• AST, ALT ≤ 2.5 × institutional ULN
• Serum sodium, potassium, calcium, magnesium, and phosphate ≥ institutional LLN. (Hypokalemia or hypomagnesemia must be corrected prior to dasatinib administration.)
• Serum creatinine 360 mg/m2 of doxorubicin or > 600 mg/m2 of epirubicin.
• Prior radiation must not have included ≥ 30% of major bone marrow containing areas (pelvis, lumbar spine).
• Patients with CTC grade 2 or greater neuropathy (motor or sensory) at study entry.
• Patient has evidence CNS or brain metastases, unless CNS or brain metastases have been treated and stable for > 3 months.
• Patient has psychiatric illness or social situation that would limit or prohibit compliance with study requirements.
• Patient has an inability to take oral medication or inability to absorb oral medication.
• Patient has had any invasive cancer other than the one being treated in this study within 3 years with the exception of surgically cured nonmelanoma skin cancer; in situ carcinoma of the cervix; in situ carcinoma of the breast.
• Patient is receiving concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, or hormonal therapy for cancer).
• Patient has other serious medical conditions as judged by the Principal Investigator.
• Patient has a concurrent medical condition which may increase the risk of toxicity.
• Patient has a pleural or pericardial effusion of any grade.
• Patient has cardiac symptoms including any of the following:
• Uncontrolled angina, congestive heart failure or myocardial infarction within 6 months of study entry.
• Diagnosed congenital long QT syndrome.
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
• Prolonged QTc on pre-entry ECG (> 450 msec).
• Hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration.
• Patient has a history of significant bleeding disorder unrelated to cancer, including:
• Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease).
• Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII