A Randomized Trial of Ixempra Versus Taxol in Adjuvant Therapy of Triple Negative Breast Cancer
A Randomized Trial of Ixempra Versus Taxol in Adjuvant Therapy of Triple Negative Breast Cancer
This is a randomized, Phase III, open-label, multicenter study.
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:

 1. Female patients greater than or equal to18 years of age.

 2. Histologically confirmed invasive unilateral breast cancer (regardless of

 histology).

 3. 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).

 4. 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.

 5. Multicentric and multifocal invasive breast cancer is eligible if loco-regional
 surgery has been completed as described above.

 6. 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.

 7. 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).

 8. Estrogen receptor negative (<10% staining by IHC for estrogen receptor).

 9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

 10. Patient must be <= 84 days from having completed definitive primary breast surgery
 (either lumpectomy or mastectomy).

 11. 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.

 12. Adequate hematologic function, defined by:

 -  Absolute neutrophil count (ANC) >1500/mm3

 -  Platelet count >=100,000/mm3

 -  Hemoglobin >9 g/dL

 13. 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).

 14. Adequate renal function, defined by:

 -  Serum creatinine <=1.5 x ULN

 15. 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.

 16. 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).

 17. 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).

 18. 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.

 19. 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.

 20. Patient must be accessible for treatment and follow-up.

 21. 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.

 22. All patients must be able to understand the investigational nature of the

 study and give written informed consent prior to study entry.

 Exclusion Criteria:

 1. Women who are pregnant or breastfeeding.

 2. 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.

 3. Any evidence or suspicion of metastatic disease other than ipsilateral

 axillary lymph nodes.

 4. Any tumor >=T4 (cutaneous invasion, deep adherence, inflammatory breast cancer).

 5. Previous anthracycline chemotherapy.

 6. Concurrent use of CYP3A4 inhibitors from 72 hours prior to initiation of

 study treatment until the end of treatment with ixabepilone.

 7. Previous treatment for this breast cancer (including neoadjuvant

 chemotherapy).

 8. 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).

 9. Peripheral neuropathy of > grade 1 per NCI CTCAE v3.0.

 10. 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.

 11. History of hypersensitivity to CremophorEL (polyoxyethylated castor oil) or

 a drug formulated in CremophorEL such as paclitaxel.

 12. Use of any investigational agent within 30 days of administration of the first dose of
 study drug.

 13. Patients may not receive any other investigational or anti-cancer treatments while
 participating in this study.

 14. 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.

 15. Mental condition that would prevent patient comprehension of the nature of, and risk
 associated with, the study.

 16. Inability to comply with study and/or follow-up procedures.