Clinical trial NCT03329378: Neoadjuvant Dose-Dense For Early Her2Neu Positive Breast Cancer
Official title: A Phase II Randomized Trial Evaluating Neoadjuvant Dose-Dense Doxorubicin/Cyclophosphamide Followed by Paclitaxel/Trastuzumab/Pertuzumab (AC THP) and Docetaxel/Carboplatin/Trastuzumab/Pertuzumab (TCHP) For Early Her2Neu Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Locally Advanced Breast Cancer
Keywords: Neoadjuvant chemotherapy
locally advanced breast cancer
Her2neu
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2017-11-06
Enrollment: 7
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 criteria: 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

Primary outcomes:
measure: Number of Participants With Pathologic Complete Response (pCR)
timeFrame: 2 years
Secondary outcomes:
measure: Number of Cardiac Toxicity Events
timeFrame: 2 years
measure: Number of Non-cardiac Toxicities
timeFrame: 2 years
measure: Number of Participants With Breast Conservation
timeFrame: 2 years
measure: Number of Participants Alive at the End of the Study
timeFrame: 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: New York
country: United States
facility: Mount Sinai West
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Aarti Bhardwaj, MD
role: PRINCIPAL_INVESTIGATOR
References: