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

Exclusion Criteria

• •1. Patient has had prior treatment with ixabepilone, dasatinib, or both.
• •2. Patient has had more than 2 prior lines of chemotherapy for locally recurrent or metastatic breast cancer. 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.
• •3. Patient has received a cumulative dose of \> 360 mg/m2 of doxorubicin or \> 600 mg/m2 of epirubicin.
• •4. Prior radiation must not have included ≥ 30% of major bone marrow containing areas (pelvis, lumbar spine).
• •5. Patients with CTC grade 2 or greater neuropathy (motor or sensory) at study entry.
• •6. Patient has evidence CNS or brain metastases, unless CNS or brain metastases have been treated and stable for \> 3 months.
• •7. Patient has psychiatric illness or social situation that would limit or prohibit compliance with study requirements.
• •8. Patient has an inability to take oral medication or inability to absorb oral medication.
• •9. 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.
• •10. Patient is receiving concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, or hormonal therapy for cancer).
• •11. Patient has other serious medical conditions as judged by the Principal Investigator.
• •12. Patient has a concurrent medical condition which may increase the risk of toxicity.
• •13. Patient has a pleural or pericardial effusion of any grade.
• •14. Patient has cardiac symptoms including any of the following:
• •1. Uncontrolled angina, congestive heart failure or myocardial infarction within 6 months of study entry.
• •2. Diagnosed congenital long QT syndrome.
• •3. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
• •4. Prolonged QTc on pre-entry ECG (\> 450 msec).
• •5. Hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration.
• •15. Patient has a history of significant bleeding disorder unrelated to cancer, including:
• •1. Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease).
• •2. Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).
• •3. Ongoing or recent (≤ 3 months) significant GI bleeding.
• •16. Patient is taking any of the following concomitant medications at study entry:
• •a. Category I drugs that are generally accepted to have a risk of causing Torsades de pointes including (Patients must discontinue drug 7 days prior to starting dasatinib.):
• •* quinidine, procainamide, disopyramide.
• •* amiodarone, sotalol, ibutilide, dofetilide.
• •* erythromycin, clarithromycin.
• •* chlorpromazine,haloperidol,mesoridazine, thioridazine,pimozide .
• •* cisapride,bepridil, droperidol, methadone, arsenic, chloroquine, domperidone,halofantrine, levomethadyl, pentamidine,sparfloxacin, lidoflazine.
• •17. Patient has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ixabepilone or dasatinib. Ixabepilone is contraindicated in patients who have a known, prior, severe (CTC grade 3 or 4) history of hypersensitivity reaction to a drug formulated in Cremophor® EL (polyoxyethylated castor oil).
• •18. Patient has received any investigational agent or therapy within 30 days prior to study treatment start.
• •19. Patient is unwilling or unable to comply with study requirements.
• •20. Women who:
• •1. are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study treatment, or
• •2. have a positive pregnancy test at baseline, or
• •3. are pregnant or breastfeeding.
• •21. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.