Neoadjuvant Dose-Dense For Early Her2Neu Positive Breast Cancer

ID#: NCT03329378

Age: 18 years - 66+

Gender: Female

Healthy Subjects: No

Study Phase: Phase 2

Recruitment Status: Recruiting

Start Date: February 01, 2019

End Date: October 16, 2019

Contact Information:
Neha Kumarley
212-824-7659
Jalwa Afroz
212-824-7320
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