Clinical Research Trials

Key Trial Criteria

• Key Inclusion Criteria

  For a patient to be eligible for participation in this study, all of the following criteria must apply.

  • The patient must have signed and dated an institutional review board (IRB)-approved consent form that conforms to federal and institutional guidelines
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination
  • All of the following staging criteria (according to the 7th edition of the American Joint Committee on Cancer [AJCC] Cancer Staging Manual) must be met:
    • By pathologic evaluation, primary tumor must be pT1-3
    • By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN2b, pN3a, or pN3b
    • If pN0, tumor must be > 3.0 cm
  • The tumor must have been determined to be human epidermal growth factor receptor 2 (HER2)-negative as follows:
    • Immunohistochemistry (IHC) 0-1+; or
    • IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to centromere enumerator probe 17 (CEP17) < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells; or
    • ISH non-amplified with a ratio of HER2 to CEP17 < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells
  • The tumor must have been determined to be estrogen receptor (ER)-and progesterone receptor (PgR)-negative assessed by current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines; patients with < 1% ER and PgR staining by IHC are considered negative
  • The patient must have undergone either a mastectomy (total, skin-sparing, or nipple-sparing) or lumpectomy
  • For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist; if pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins; if tumor is still present at the resected margin after re-excision(s), the patient must undergo mastectomy to be eligible; (patients with margins positive for lobular carcinoma in situ [LCIS] are eligible without additional resection)
  • For patients who undergo mastectomy, the margins must be free of residual gross tumor; (patients with microscopic positive margins are eligible as long as post-mastectomy radiation therapy [RT] of the chest wall will be administered)
  • The patient must have completed one of the procedures for evaluation of pathologic nodal status listed below.
    • Sentinel lymphadenectomy alone:
      • If pathologic nodal staging based on sentinel lymphadenectomy is pN1mi or pN1a and the patient has undergone breast-conserving surgery (with planned breast radiotherapy), the primary tumor must be T1 or T2 by pathologic evaluation and the nodal involvement must be limited to 1 or 2 positive nodes
      • If pathologic nodal staging based on sentinel lymphadenectomy is pN0 or pN1b;
      • Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes if the sentinel node (SN) is positive; or
      • Axillary lymphadenectomy with or without SN isolation procedure
  • The interval between the last surgery for breast cancer (including re-excision of margins) and randomization must be no more than 60 days
  • Absolute neutrophil count (ANC) must be >= 1200/mm^3
  • Platelet count must be >= 100,000/mm^3
  • Hemoglobin must be >= 10 g/dL
  • Total bilirubin must be =< upper limit of normal (ULN) for the laboratory (lab) unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin
  • Alkaline phosphatase must be =< 2.5 x ULN for the lab
  • Aspartate aminotransferase (AST) must be =< 1.5 x ULN for the lab
    • Note: If alanine aminotransferase (ALT) is performed instead of AST (per institution's standard practice), the ALT value must be =< 1.5 x ULN; if both were performed, the AST must be =< 1.5 x ULN
  • Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (computed tomography [CT], magnetic resonance imaging [MRI], positron emission tomography [PET]-CT, or PET scan) performed within 90 days prior to randomization does not demonstrate metastatic disease and the requirements above are met
  • Patients with alkaline phosphatase that is > ULN but =< 2.5 x ULN or unexplained bone pain are eligible for inclusion in the study if a bone scan, PET-CT scan, or PET scan performed within 90 days prior to randomization does not demonstrate metastatic disease
  • Adequate renal function determined within 6 weeks prior to randomization defined as the most recent serum creatinine =< ULN or measured or calculated creatinine clearance > 60 mL/min
  • Left ventricular ejection fraction (LVEF) assessment must be performed within 90 days prior to randomization; (LVEF assessment performed by 2-dimensional [D] echocardiogram is preferred; however, multi-gated acquisition [MUGA] scan may be substituted based on institutional preferences;) the LVEF must be >= 50% regardless of the cardiac imaging facility's lower limit of normal

• Key Exclusion Criteria

  A patient will not be eligible for participation in this study if any of the following criteria apply.

  • T4 tumors including inflammatory breast cancer
  • Definitive clinical or radiologic evidence of metastatic disease; required imaging studies must have been performed within 90 days prior to randomization
  • Synchronous or previous contralateral invasive breast cancer; (patients with synchronous and/or previous contralateral DCIS or LCIS are eligible)
  • Any previous history of ipsilateral invasive breast cancer or ipsilateral DCIS; (patients with synchronous or previous ipsilateral LCIS are eligible)
  • History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization
  • Previous therapy with anthracyclines or taxanes for any malignancy
  • Chemotherapy administered for the currently diagnosed breast cancer prior to randomization
  • Any continued use of sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy; patients are eligible if these medications are discontinued prior to randomization
  • Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens; this includes but is not confined to:
    • Active cardiac disease
      • Symptomatic pericarditis
      • Valvular disease with documented compromise in cardiac function; or
      • Conduction abnormality requiring a pacemaker;
      • Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication;
      • Ventricular arrhythmias except for benign premature ventricular contractions;
      • Angina pectoris that requires the current use of anti-anginal medication;
      • History of cardiac disease
        • Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricle (LV) function;
        • History of documented congestive heart failure (CHF); or
        • Documented cardiomyopathy
  • Uncontrolled hypertension defined as sustained systolic blood pressure (BP) > 150 mmHg or diastolic BP > 90 mmHg; (patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria)
  • Active hepatitis B or hepatitis C with abnormal liver function tests
  • Patients known to be human immunodeficiency virus (HIV) positive with a baseline cluster of differentiation (CD)4 count of < 250 cells/mm^3 or have a history of acquired immune deficiency syndrome (AIDS) indicator conditions
  • Intrinsic lung disease resulting in dyspnea
  • History of hospitalization in past 12 months for diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic nonketotic syndrome (HHNS)
  • Active infection or chronic infection requiring chronic suppressive antibiotics
  • Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) >= grade 2, per the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0
  • Conditions that would prohibit administration of corticosteroids
  • Chronic daily treatment with corticosteroids with a dose of >= 10 mg/day methylprednisolone equivalent (excluding inhaled steroids)
  • Known hypersensitivity to any of the study drugs or excipients, e.g., polysorbate 80 and Cremophor® EL
  • Other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up
  • Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
  • Pregnancy or lactation at the time of study entry; (note: pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to randomization)
  • Use of any investigational product within 4 weeks prior to randomization