Patient case: 70-year-old female with breast cancer; genetic feature: AURKA amplification

Clinical trial: Neoadjuvant Dose-Dense For Early Her2Neu Positive Breast Cancer

Summary: Primary Objective:
  • Determination of pathologic complete response (pCR) rates
  Secondary Objective:
  -  Determination of cardiac toxicity as measured by: composite of LVEF, longitudinal strain and troponin.
  -  Breast conservation rates
  -  Overall survival
  Study Design
  -  Approximately 34-74 patients with Her2 positive, Stage II-regional IV breast cancer will be enrolled.
  -  Patients will be stratified by ER/PR status.
  -  They will be randomized to ddACTHP vs TCHP.
  -  Initially, 17 patients will be randomly assigned to each treatment arm.
  -  If 3 or fewer patients have a pCR, then that arm will be terminated and no further patients will be entered on that treatment arm.
  -  If 4 or more patients obtain a pCR, 20 additional patients (total of 37 patients) will be randomized to that treatment arm.
  -  If 11 or more patients out of 37 have a pCR, the treatment will be of interest for further study.


Eligibility: Inclusion Criteria:
  The patient must have signed and dated an IRB-approved consent form that conforms to federal and institutional guidelines.
  -  Female
  -  18 years or older
  -  ECOG performance status of 0 or 1
  -  Eligible tumors must meet one of the following criteria:
  -  Operable (T1c, T2-3, N0-1, M0)
  -  Locally advanced (T2-3, N2-3, M0 or T4a-c, any N, M0)
  -  Inflammatory breast cancer (T4d, any N, M0)
  -  Staging evaluation:
  -  History and physical exam, cbc, chemistry profile
  -  CT Chest/Abdomen/Pelvis and a bone scan or PET/CT as needed
  -  Diagnosis of invasive adenocarcinoma made by core needle biopsy
  -  Breast cancer determined to be:
  -  Confirmed HER2-positive : (ASCO CAP guidelines, 10/7/2013)
  -  IHC 3+ based on circumferential membrane staining that is complete, intense
  -  ISH positive based on:
  -  Single probe average HER2 copy number ≥ 6 signals/cell
  -  Dual probe HER2/CEP 17 ratio ≥ 2.0 with an average HER2 copy number ≥ 4.0 signals/cell
  -  Dual probe HER2/CEP 17 ratio ≥ 2.0, with an average HER2 copy number of < 4.0 signals/cell
  -  Dual probe HER2/CEP 17 ratio < 2.0 with the average HER2 copy number of ≥ 6.0 signals/cell
  -  any ER or PR receptor status
  -  LVEF assessment by echocardiogram within 30 days of initiation; EF of ≥ 55% considered normal.
  -  Normal troponin I level at baseline
  -  Blood counts must meet the following criteria:
  -  ANC greater than or equal to 1500/mm3
  -  Platelet count greater than or equal to 100,000/mm3
  -  Hemoglobin greater than or equal to 10 g/dL
  -  Serum creatinine less than or equal 2.5 mg/100ml
  -  Adequate hepatic function by these criteria: total bilirubin must be less than or equal to 1.5 x the ULN for the lab unless the patient has a bilirubin elevation great than the ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab; and AST must be less than or equal to 1.5 x ULN for the lab. Both alkaline phosphatase and AST may not both be greater than the ULN.
  -  Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (CT, MRI, PET-CT or PET scan) performed within 90 days prior to randomization does not demonstrate metastatic disease and the requirements are met as above
  -  Patients with alkaline phosphatase that is > ULN but less than or equal to 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.
  Exclusion Criteria:
  Patients with a history of decompensated congestive heart failure or an EF < 55% will be excluded
  • Cardiac disease that would preclude the use of the drugs included in the above regimens. This includes but is not confined to:
  -  Active cardiac disease:
  -  angina pectoris requiring the use of anti-anginal medication;
  -  ventricular arrhythmias except for benign premature ventricular contractions controlled by medication;
  -  conduction abnormality requiring a pacemaker;
  -  supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; and
  -  clinically significant valvular disease
  -  symptomatic pericarditis
  -  pulmonary hypertension
  -  History of cardiac disease:
  -  myocardial infarction;
  -  congestive heart failure; or
  -  cardiomyopathy

Relevance to patient case: not relevant