A Phase II Study of CI-1033 in Treating Patients With Metastatic (Stage IV) Breast Cancer

Inclusion Criteria:

• Female, at least 18 years of age
• Histologically confirmed diagnosis of breast cancer
• Metastatic (Stage IV) disease
• Progressive or recurrent disease following the most recent therapy
• No more than 2 different, prior cytotoxic chemotherapy regimens for metastatic disease
• At least one measurable target lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) that has not been irradiated
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, determined within 2 weeks prior to randomization
• Estimated life expectancy of > 12 weeks
• Capable of giving written informed consent
• Capable of swallowing intact CI-1033 capsules
• Capable of understanding and adhering to the protocol requirements
• No prior exposure to CI-1033 or other agents that target the erbB receptor family (such as Herceptin, Iressa, Tarceva, IMC-C225, and EKB-569)
• No known hypersensitivity reaction to tyrosine kinase inhibitors
• Adequate liver, renal, or bone marrow function determined within 2 weeks prior to randomization
• No cytotoxic chemotherapy within 3 weeks prior to baseline disease assessments (6 weeks for nitrosoureas or mitomycin)
• No immunotherapy (including Herceptin) or other biologic therapy within 2 weeks prior to baseline disease assessments
• No hormone therapy (including hormone replacement therapy) within 4 weeks prior to baseline disease assessments (6 weeks for megestrol acetate)
• Patients must have recovered from the acute effects of any radiation therapy or surgery
• No treatment with any other investigational therapy within 4 weeks prior to baseline disease assessments
• No history of any cancer other than the present condition (except nonmelanoma skin cancer or carcinoma in situ of the cervix) within the last 5 years
• No patients with untreated brain metastases or patients that have not recovered from treatment for brain metastases
• No known malabsorption syndrome or other condition that may impair absorption of study medication
• No comorbidity or condition which compromises compliance with this protocol as judged by the investigator or that would significantly complicate interpretation of the safety profile of CI-1033
• No patients having reproductive potential who are not using a method of birth control or who are pregnant or breastfeeding or have a positive pregnancy test during baseline

Exclusion Criteria:

Prior exposure to CI-1033 or other agents that target the erbB receptor family; cytotoxic chemotherapy within 3 weeks prior to baseline disease assessments (6 weeks for nitrosoureas or mitomycin); immunotherapy (including Herceptin) or other biologic therapy within 2 weeks prior to baseline disease assessments; hormone therapy (including hormone replacement therapy) within 4 weeks prior to baseline disease assessments; 6 weeks for megestrol acetate (to exclude the possibility of a hormone-withdrawal response); patients with untreated brain metastases.