Trial of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Locally Advanced HER2-Negative Breast Cancer

Inclusion Criteria

• Histologically confirmed invasive adenocarcinoma of the breast.
• Primary palpable disease confined to the breast and axilla on physical examination (clinical Stage II or III disease). For patients without clinically suspicious axillary adenopathy, the primary must be >2 cm in diameter by physical examination or imaging studies (clinical T2-3, N0-2, M0). For patients with clinically suspicious axillary adenopathy, the primary breast tumor can be any size (clinical T1-3, N1-2, M0). Patients who have had axillary node dissection and have pN3a (i.e. ≥10 involved axillary nodes) are also eligible.
• Patients entering the trial after undergoing an axillary node dissection will be eligible if they meet other entry criteria.
• Estrogen receptor (ER) and progesterone receptor (PR) status in the primary tumor known or pending at the time of study registration.
• Resolution of all acute effects of surgical procedures to ≤ grade 1. For patients who had or will have, a sentinel node and/or axillary node dissection, completion at least 1 week prior to the initiation of study treatment with a well-healed wound is required.
• Bilateral, synchronous breast cancer is allowed if both primary tumors are HER2-negative and at least one meets the specified qualifying tumor or nodal inclusion criteria.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-2.
• Patients entering this study must be willing to provide release of tumor tissue collected at baseline during a diagnostic procedure if available, and at the time of future surgical procedure(s) for correlative testing. If tissue is not available, the patient will still be eligible for enrollment to the study.
• No evidence of metastatic disease, as documented by complete staging workup ≤8 weeks prior to initiation of study treatment.
• No prior treatment for this breast cancer with the exception of criterion #3.
• HER2-negative tumor status defined as:
• Immunohistochemical (IHC) 0-1+ or
• IHC 2+ or IHC 3+ confirmed as FISH (Fluorescence in situ hybridization) or SISH (Silver in situ hybridization) negative (defined by ratio grade 1 according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
• Patient has received radiotherapy for treatment of previous cancer that included ≥30% of major bone marrow containing areas (e.g., pelvis, lumbar, spine).
• Known or suspected allergy or hypersensitivity to any of the study drugs (i.e., eribulin, cyclophosphamide, docetaxel) or known hypersensitivity to polysorbate 80.
• Patients with acute or chronic liver or renal disease or pancreatitis.
• Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV).
• Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator (SERM). Patients must have discontinued use of such agents prior to beginning study treatment. However, use of GNRH agonists for the purpose of fertility preservation or suppression of heavy menses is permitted (see Section 5.4.1).
• Patient has any of the following cardiac diseases currently or within the last 6 months:
• Left Ventricular Ejection Fraction (LVEF) 480 ms on screening electrocardiogram (ECG) (using Bazett's formula)
• Unstable angina pectoris
• Congestive heart failure (New York Heart Association [NYHA] ≥ Grade 2
• Acute myocardial infarction
• Conduction abnormality not controlled with pacemaker or medication
• Significant ventricular or supraventricular arrhythmias (Patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
• Valvular disease with significant compromise in cardiac function
• Chronic use of drugs that cause QTc prolongation. Patients must discontinue use of these drugs 7 days prior to the start of study treatment.
• Presence of other active cancers, or history of treat