Ixabepilone and Cyclophosphamide as Neoadjuvant Therapy in HER-2 Negative Breast Cancer

Inclusion Criteria

• Female patients, age ≥18 years.
• Histologically confirmed invasive adenocarcinoma of the breast.
• Primary palpable disease confined to a breast and axilla on

physical examination. For patients without clinically suspicious

axillary adenopathy, the primary tumor must be larger than 2 cm

in diameter by physical exam or imaging studies (clinical T2-T3,

N0-N1, M0). For patients with clinically suspicious axillary

adenopathy, the primary breast tumor can be any size (clinical

T1-3, N1-2, M0). (T1N0M0 lesions are excluded.)

• Patients without clearly defined palpable breast mass or axillary

lymph nodes but radiographically measurable tumor masses are

acceptable. Accepted procedures for measuring breast disease

are mammography, MRI, and breast ultrasound. This will need to

be re-evaluated after 3 cycles and prior to surgery.

• Eastern Cooperative Oncology Group performance status (ECOG

PS) 0-2.

• No metastatic disease, as documented by complete staging workup
• 6 weeks prior to initiation of study treatment.
• No previous treatment for breast cancer.
• HER2-negative tumor status. HER2-negative is defined as:
• Immunohistochemical (IHC) 0, IHC 1+ OR
• IHC 2+ or IHC 3+ must be confirmed as FISH (fluorescence in situ

hybridization) negative (defined by ratio 1500/μL.

• Platelets ≥100,000/μL.
• Hemoglobin ≥10 g/dL.
• Adequate hepatic function with:
• Serum bilirubin ≤ the institutional upper limit of normal (ULN).
• Aspartate aminotransferase (AST) ≤2.5 x institutional ULN.
• Alanine aminotransferase (ALT) ≤2.5 x institutional ULN.
• Adequate renal function with serum creatinine ≤1.5 x ULN.
• Estrogen and progesterone receptor status in the primary tumor

known or pending at the time of study registration.

• Knowledge of the investigational nature of the study and ability to

provide consent for study participation.

• For patients who had, or will have sentinel lymph node and/or

axillary dissection prior to initiation of study treatment, completion

at least 4 weeks prior to starting study treatment and well-healed

wound

• Bilateral, synchronous breast cancer is allowed if one primary

tumor meets the inclusion criteria.

• Sufficient archived breast tumor specimen available at baseline

for the Oncotype DX assay.

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Exclusion Criteria

• Inflammatory breast cancer.
• Peripheral neuropathy (motor or sensory) ≥ grade 1 by the

Common Terminology Criteria for Adverse Events version 3.0

(CTCAE v 3.0).

• Prior radiation that included ≥30% of major bone marrow containing

areas (pelvis, lumbar, spine).

• Chronic use of cytochrome P450 (CYP) 3A4 inhibitors and use of

the following strong CYP3A4 inhibitors: ketoconazole,

itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir,

telithromycin, ritonavir, amprenavir, indinavir, nelfinavir,

delavirdine, and voriconazole. Use of these agents should be

discontinued at least 72 hours prior to initiation of study treatment.

• Chemotherapy within 5 years of starting study treatment except

for low doses of agents used for anti-inflammatory indications

such as rheumatoid arthritis, psoriasis, and connective tissue

disorders. Although such doses and schedules cannot result in

myelosuppression, patients must discontinue this therapy while

they are receiving study treatment.

• Known or suspected hypersensitivity to Cremophor®EL

(polyoxyethylated castor oil) or a drug formulated in

Cremophor®EL such as paclitaxel, or any other agent given in the

course of this study.

• Pregnancy or breast-feeding. A negative serum pregnancy test

within 7 days prior to first study treatment (Day 1, Cycle 1) for all

women of childbearing potential is required. Patients of

childbearing potential must agree to use a birth control method

that is approved by their study physician while receiving study

treatment and for 3 weeks after their last dose of study treatment.

Patients must agree to not breast-feed while receiving study

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