Clinical Trials /

Neoadjuvant Dose-Dense For Early Her2Neu Positive Breast Cancer

NCT03329378

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: GCO 17-1585
  • NCT ID: NCT03329378

Conditions

  • Locally Advanced Breast Cancer

Interventions

DrugSynonymsArms
DocetaxelTCHP
CarboplatinTCHP
TrastuzumabTCHP
PertuzumabddACTHP
PegfilgrastimTCHP
TrastuzumabddACTHP
PaclitaxelddACTHP
DoxorubicinddACTHP
CyclophosphamideddACTHP
PaclitaxelddACTHP

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
ddACTHPActive ComparatorDoxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Pegfilgrastim 6mg SC, day 2 of AC Cycled every 14 days for 4 cycles, followed by, Paclitaxel 80 mg/m2 IV x 1 hour infusion on days 1, 8, and 15 Trastuzumab 8 mg/kg IV day 1, followed by 6mg/kg Pertuzumab loading dose 840 mg IV followed by 420 mg IV every 3 weeks Cycled every 21 days for 4 cycles, followed by, Trastuzumab 6mg/kg every 21 days to complete 1 year
  • Pertuzumab
  • Trastuzumab
  • Paclitaxel
  • Doxorubicin
  • Cyclophosphamide
  • Paclitaxel
TCHPActive ComparatorTCHP (Docetaxel, Carboplatin, Trastuzumab, Pertuzumab, Pegfilgrastim ) institutional practice is to titrate the infusion rate on the initial Paclitaxel dose (40 ml/hr x 5 min, then 80 ml/hr x 5 min, then 120 ml/hr x 10 min, then 200 ml/hr). Subsequent Paclitaxel doses are given over 1 hour.
  • Docetaxel
  • Carboplatin
  • Trastuzumab
  • Pertuzumab
  • Pegfilgrastim
  • Trastuzumab
  • Paclitaxel

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:pCR rates
Time Frame:up to 2 years
Safety Issue:
Description:Pathologic complete response (pCR) defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of neoadjuvant systemic therapy.

Secondary Outcome Measures

Measure:Cardiac Toxicity
Time Frame:up to 2 years
Safety Issue:
Description:Determination of cardiac toxicity as measured by: composite of LVEF, longitudinal strain and troponin. Left ventricular ejection fraction (LVEF) measurement of amount of blood being pumped out of the left ventricle of the heart with each contraction. Peak systolic longitudinal strain is calculated by averaging the values of peak systolic strain in the basal, mid and apical segments of the LV in 4-, 3- and 2-chamber views on echocardiograms. A value of <-18% or a >15% decline in strain from patient's baseline value will be used as a cut-off value. A value of troponin I > 0.08 ng/ml 21, 30,31 will be considered elevated.
Measure:Number of non-cardiac toxicities
Time Frame:up to 2 years
Safety Issue:
Description:The frequency of adverse events categorized using CTCAE v4.03
Measure:Breast Conservation Rates
Time Frame:up to 2 years
Safety Issue:
Description:rate of breast-conserving surgery for patients for whom mastectomy was planned before treatment. It would be based on surgical opinion at time of surgery if the tumor was appropriately "downstaged" to perform breast conserving surgery on patients previously recommended to have a mastectomy.
Measure:Overall Survival
Time Frame:up to 2 years
Safety Issue:
Description:Overall Survival Rate

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Icahn School of Medicine at Mount Sinai

Trial Keywords

  • Neoadjuvant chemotherapy
  • locally advanced breast cancer
  • Her2neu

Last Updated

October 30, 2017