Phase I Study of Ixabepilone Plus Lapatinib With or Without Capecitabine in the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer

Parallel Phase I Study of Ixabepilone Plus Lapatinib and Ixabepilone Plus Lapatinib Plus Capecitabine in Subjects With HER2 Positive Locally Advanced or Metastatic Breast Cancer

The purpose of this study is to determine the safety and preliminary effectiveness of ixabepilone plus lapatinib with and without capecitabine in the treatment of human epidermal growth factor receptor 2 (HER2)-positive or metastatic breast cancer.

Inclusion Criteria:

• Females aged 18 years or older with histologic or cytologic diagnosis of adenocarcinoma originating in the breast
• Radiologic or pathologic evidence that the cancer is metastatic or locally advanced (a T4 tumor and stage IIIB/IIIC disease) and not curable by local measures, such as radiation or surgery
• Positive status for human epidermal growth factor receptor 2
• Measurable disease as per Response Evaluation Criteria In Solid Tumors guidelines
• Karnofsky performance status of 70 to 100
• Life expectancy of at least 3 months

Exclusion Criteria:

• Prior radiation must not have included 30% or more of major bone-marrow containing areas, such as the pelvis and lumbar spine
• Common Terminology Criteria Grade 2 or greater neuropathy
• Inadequate hematologic, hepatic, or renal function
• Known prior severe hypersensitivity reactions to agents containing Cremophor® EL or known hypersensitivity or prior intolerance to fluoropyrimidine
• Known or suspected dihydropyrimidine dehydrogenase deficiency
• More than 3 prior chemotherapy regimens in the metastatic setting
• Prior treatment with an epothilone or lapatinib; prior treatment with capecitabine within the past 6 months