A Randomized Trial of Ixempra Versus Taxol in Adjuvant Therapy of Triple Negative Breast Cancer

Patients will be randomized in a 1:1 ratio to receive one of two different treatment arms. Patients in treatment arm 1 will receive AC followed by ixabepilone. Patients in treatment arm 2 will receive AC followed by weekly paclitaxel.

Inclusion criteria

• Female patients greater than or equal to18 years of age.
• Histologically confirmed invasive unilateral breast cancer (regardless of

histology).

• Early-stage breast cancer, defined as:

• Node-positive disease: >0.2-mm metastasis in at least one lymph node (pN1mipN2b)OR
• Node-negative, with primary tumor >1.0 cm (T1c-T3).
• Definitive loco-regional surgery must have been completed as specified

below:

• Patients must have undergone either breast conservation surgery

(i.e., lumpectomy) or total mastectomy.

• Surgical margins of the resected section must be histologically free of

invasive adenocarcinoma and ductal carcinoma in situ.

• Surgical margins involved with lobular carcinoma in situ (LCIS) will not

be considered as a positive margin; therefore, such patients will be eligible for this study without additional resection.

• Patients must have completed axillary lymph node sampling for the pathologic evaluation of axillary lymph nodes as specified below:

Sentinel node biopsy and/or either lymph node sampling procedure or axillary dissection.

• Multicentric and multifocal invasive breast cancer is eligible if loco-regional surgery has been completed as described above.
• Patients with synchronous bilateral cancers are eligible only if:

• All cancers are of triple-negative phenotype, defined as ER-, PR-, HER2-.
• Eligibility based on the highest stage grouping.
• HER2 negative tumors. HER2 negativity must be confirmed by one of the

following:

• FISH-negative (FISH ratio <2.2), or
• IHC 0-1+, or
• IHC 2-3+ AND FISH-negative (FISH ratio <2.2).
• Estrogen receptor negative (<10% staining by IHC for estrogen receptor).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Patient must be <= 84 days from having completed definitive primary breast surgery (either lumpectomy or mastectomy).
• MammoSite brachytherapy radiation is acceptable if it is performed

immediately following surgery and prior to chemotherapy. It is recommended that chemotherapy be started no earlier than 2 weeks following the removal of the MammoSite balloon catheter.

• Adequate hematologic function, defined by:

• Absolute neutrophil count (ANC) >1500/mm3
• Platelet count >=100,000/mm3
• Hemoglobin >9 g/dL
• Adequate liver function, defined by:

• AST and ALT <=2.5 x the upper limit of normal (ULN)
• Total bilirubin <=1.5 x ULN (unless the patient has grade 1 bilirubin

elevation due to Gilbert's disease or a similar syndrome involving slow

conjugation of bilirubin).

• Adequate renal function, defined by:

• Serum creatinine <=1.5 x ULN
• Complete staging work-up <=12 weeks prior to initiation of study treatment

with computed tomography (CT) scans of the chest and abdomen/pelvis (abdomen/pelvis preferred; abdomen accepted), and either a positron emission tomography (PET) scan or a bone scan.

• Adequate cardiac function, defined by a left ventricular ejection fraction

(LVEF) value of >50% (or normal per institutional guidelines) by MUGA scan or echocardiogram (ECHO).

• Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of a minor surgery (i.e., sentinel node biopsy, port-acath (placement); at least 3 weeks must have elapsed from the time of a major surgery (i.e., lumpectomy, partial or total mastectomy, axillary lymph node dissection, breast reconstruction procedure).
• Patients with previous history of invasive cancers (including breast cancer)

are eligible if definitive treatment was completed more than 5 years prior to

initiating current study treatment, and there is no evidence of recurrent disease.

• Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
• Patient must be accessible for treatment and follow-up.
• Women of childbearing potential must agree to use an acceptable method of birth control to avoid pregnancy for the duration of study treatment, and for 3 months thereafter.
• All patients must be able to understand the investigational nature of the

study and give written informed consent prior to study entry.

Exclusion criteria

• Women who are pregnant or breastfeeding.
• History of previous diagnosis of invasive breast cancer (unless treated >5 years previously with no recurrence). History of previously treated ductal carcinoma in situ (DCIS) is acceptable.
• Any evidence or suspicion of metastatic disease other than ipsilateral

axillary lymph nodes.

• Any tumor >=T4 (cutaneous invasion, deep adherence, inflammatory breast cancer).
• Previous anthracycline chemotherapy.
• Concurrent use of CYP3A4 inhibitors from 72 hours prior to initiation of

study treatment until the end of treatment with ixabepilone.

• Previous treatment for this breast cancer (including neoadjuvant

chemotherapy).

• Previous cancer (with the exception of non-melanoma skin cancer or cervical carcinoma in situ) in the past 5 years (including invasive contralateral breast cancer).
• Peripheral neuropathy of > grade 1 per NCI CTCAE v3.0.
• Cardiac disease, including: congestive heart failure (CHF) > Class II per

New York Heart Association (NYHA) classification; unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months; symptomatic CHF, unstable angina pectoris, cardiac arrhythmia, or cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

• History of hypersensitivity to CremophorEL (polyoxyethylated castor oil) or

a drug formulated in CremophorEL such as paclitaxel.

• Use of any investigational agent within 30 days of administration of the first dose of study drug.
• Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
• Concurrent severe, uncontrolled infection or intercurrent illness including,

but not limited to, ongoing or active infection, or psychiatric illness/social

situations that would limit compliance with study requirements.

• Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
• Inability to comply with study and/or follow-up procedures.