Neo-Adjuvant Study in Triple Negative Breast Cancer Patients

Ixabepilone and capecitabine combination has demonstrated to be an active regimen in patients
with metastatic breast cancer (MBC) after failing an anthracycline and a taxane regimen.
Cetuximab is active in tumors that express epidermal growth factor receptor (EGFR) with
demonstrated activity in head and neck and colorectal tumors. A proportion of breast cancers
are known to express EGFR. Cetuximab's mechanism of action suggests the possibility of
efficacy in breast cancer patients, and several studies show that it may be efficacious in
Triple Negative Breast Cancer (TNBC). This study seeks to evaluate Ixabepilone alone or in
combination with cetuximab as a possible way to increase antitumor activity. In this
randomized open-label phase II trial, patients will be randomized equally between 1)
Ixabepilone or 2) Ixabepilone plus Cetuximab. Randomization will be stratified by disease
stage (T1N1-3M0 or T2-4 N0-3M0).

The study's primary objective is to determine the pathologic complete response rate (pCR)
(breast and axilla) of Ixabepilone versus Ixabepilone when combined with cetuximab in
patients with invasive breast adenocarcinoma T1N1-N3M0 or T2-4 N0-3M0 disease who are triple
negative and who are candidates for preoperative chemotherapy. The secondary objectives are
to evaluate overall objective response rate in both treatment groups and to assess safety and
toxicity of each regimen. There are also tertiary, exploratory objectives that will hopefully
allow for the correlation of biomarker expression and response to treatment.

Inclusion Criteria:

- Patients with histologic confirmation of invasive breast carcinoma.

- Patients must have intact primary tumor.

- Patients greater than or equal to 18 years.

- Patients should have T1N1-3M0 or T2-4 N0-3M0.

- Patients with bilateral breast cancer are eligible.

- Patients with second primary breast cancers are eligible.

- Patients should have a Karnofsky performance scale of greater than or equal to 70%.

- Patients must have clinically measurable disease to be treated in the neoadjuvant
setting.

- Patients should have adequate bone marrow function, as defined by peripheral
granulocyte count of greater than or equal to 1500/mm^3, and platelet count greater
than or equal to 100000mm^3.

- Patients must have adequate liver function with a bilirubin within normal laboratory
values. Alkaline phosphatase and transaminases (ALT and AST) may be up to 1.5 x upper
limit of normal (ULN) of the institution.

- Patients should have adequate renal function with creatinine levels within normal
range.

- Patients should have a normal left ventricular ejection fraction (LVEF) of greater
than or equal to 50%.

- Negative serum or urine pregnancy test for a woman of childbearing potential (WOCBP).

- WOCBP must use a reliable and appropriate contraceptive method during the study and
six months after chemotherapy is completed. WOCBP are women who are not menopausal for
12 months or had no previous surgical sterilization.

- Patients must agree to have study biopsies.

- Patients must sign an informed consent indicating that they are aware of the
investigational nature of the study, in keeping with institutional policy.

Exclusion Criteria:

- Patients with a history of other invasive malignancies diagnosed and treated within
the previous 5 years, except non-melanoma skin cancer and non-invasive cervical
cancer.

- Her2Neu, ER and PR positive patients should be excluded.

- Patients with Inflammatory breast cancer (IBC) are excluded.

- Patients with an organ allograft or other history of immune compromise.

- Prior treatment with any investigational drug within the preceding 4 weeks.

- Chronic treatment with systemic steroids or another immunosuppressive agent.

- A Known history of HIV seropositivity.

- Patients with an active, bleeding diathesis or on oral anti-vitamin K medication
(except low dose coumarin defined as 1 mg a day).

- Other concurrent and/or uncontrolled medical disease which could compromise
participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension,
severe infection, severe malnutrition, unstable angina, or congestive heart failure -
New York Heart Association Class III or IV, ventricular arrhythmias, active ischemic
heart disease, myocardial infarction within six months, chronic liver or renal
disease, active upper GI tract ulceration).

- Patients with a pre-existing peripheral neuropathy.