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

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