Neoadjuvant Ixabepilone/Carboplatin/Trastuzumab in HER2-Positive Locally Advanced Breast Cancer

Exclusion Criteria

• •1. Previous treatment for this breast cancer.
• •2. Evidence of metastatic disease.
• •3. Prior radiation that included ≥30% of major bone marrow-containing areas.
• •4. Women who are pregnant or breastfeeding.
• •5. Neuropathy (motor or sensory) ≥grade 1 at study entry.
• •6. History of significant cardiac disease or cardiac risk factors or the following:
• •* uncontrolled arrhythmias
• •* poorly controlled hypertension (e.g., systolic blood pressure \[BP\]\> 150 mmHg or diastolic BP \>100 mmHg) in spite of optimal medical management
• •* angina pectoris requiring antianginal medication or unstable angina within the previous 6 months
• •* history of documented congestive heart failure (CHF)
• •* any documented myocardial infarction within the previous 6 months
• •* clinically significant valvular heart disease
• •* current use of medications (e.g., digitalis, beta-blockers, calcium channel-blockers) that alter cardiac conduction, if these medications are administered for the management of cardiac arrhythmia, angina, or CHF. If these medications are administered for other reasons (e.g., hypertension), the patient may be eligible.
• •* patients with cardiomegaly on chest x-ray or ventricular hypertrophy on ECG unless ECHO or MUGA scan within the last 3 months demonstrates that the LVEF is ≥ institutional lower limit of normal.
• •7. Symptomatic intrinsic lung disease.
• •8. Active malignancy, other than superficial basal cell carcinoma, superficial squamous (skin) cell carcinoma, carcinoma in situ, or non-invasive breast cancer, within the past 5 years.
• •9. Uncontrolled intercurrent illness including (but not limited to) ongoing or active infection \>grade 2.
• •10. Mental condition or psychiatric disorder rendering the subject unable to understand the nature, scope, and possible consequences of the study or that would limit compliance with study requirements.
• •11. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving a reasonable suspicion of a disease or condition that contraindicates the use of a study agent or that may affect the interpretation of the results or renders the subjects at high risk from treatment complications.
• •12. Chronic use of CYP3A4 inhibitors and use of the following strong CYP3A4 inhibitors: ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine, and voriconazole. Use of these agents must be discontinued at least 72 hours prior to initiation of study treatment.
• •13. Received chemotherapy for any indication within the 5 years preceding study enrollment.
• •14. Prior treatment with trastuzumab or any other anti-HER2 agent for any indication.
• •15. Concurrent treatment with any other anti-cancer therapy.
• •16. Concurrent radiation therapy during neoadjuvant study treatment.
• •17. Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment must be stopped prior to study enrollment.
• •18. Current therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or prevention of breast cancer. These agents must be discontinued prior to study enrollment.
• •19. Participation within the previous 30 days in a study with an experimental drug.
• •20. Known or suspected allergy to Cremophor EL (polyoxyethylated castor oil), a drug formulated in Cremophor EL such as paclitaxel, or any other agent given in the course of this trial.
• •21. Inability or unwillingness to comply with study procedures including those for follow-up.