Ixabepilone and Vorinostat in Treating Patients With Metastatic Breast Cancer

PRIMARY OBJECTIVES: I. To determine the safety and tolerability of the combination of vorinostat with ixabepilone. II. To determine the best schedule for delivery of this drug combination. III. To recommend a phase II dose of vorinostat in combination with ixabepilone. SECONDARY OBJECTIVES: I. To determine the objective response rate and/or clinical benefit rate. II. To assess the toxicity profile. TERTIARY OBJECTIVES: I. Collecting circulating tumor cells pre and post-treatment to study its deoxyribonucleic acid (DNA) somatic mutation and methylation assay after the introduction of histone deacetylases (HDAC) inhibitors and ixabepilone. II. To determine whether administration of vorinostat with ixabepilone will alter the pharmacokinetics of vorinostat. OUTLINE: This is a phase I, dose-escalation study of vorinostat. Patients are randomized to 1 of 2 treatment arms. Arm I (Cohort A): Patients receive oral vorinostat once daily on days 1-14 and ixabepilone intravenously (IV) over 3 hours on day 2. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm II (Cohort B): Patients receive oral vorinostat once daily on days 1-7 and 15-21. Patients also receive ixabepilone IV over 3 hours on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.