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