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

A Phase II, Randomized, Open-Label Study of Single Agent CI-1033 in Patients With Metastatic Breast Cancer

CI-1033 is an experimental drug that acts as an inhibitor of erbB (EGFR) receptors, which may be involved in tumor growth. The primary objective of this study is to assess the antitumor activity of CI-1033 in patients with metastatic breast cancer. Patients with histologically confirmed metastatic (Stage IV) breast cancer and who have received no more than 2 prior cytotoxic chemotherapy regimens are eligible for this study. CI-1033 is administered orally. Patients are required to have blood tests periodically while receiving treatment and will be closely monitored throughout the study for possible side effects and response to treatment. Patients may not have received any prior treatment with other agents that target erbB receptors, including Herceptin (trastuzumab) or Iressa (gefitinib).

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.