Neoadjuvant Dose-Dense For Early Her2Neu Positive Breast Cancer

NCT ID: NCT03329378

Last Updated: 2023-08-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-24
• Study Completion Date: 2021-03-07

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.

Conditions

Locally Advanced Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ddACTHP

Doxorubicin 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

Group Type: ACTIVE_COMPARATOR

Pertuzumab

Intervention Type: DRUG

Pertuzumab 840 mg IV initial dose followed by 420 mg IV, day 1

Trastuzumab

Intervention Type: DRUG

Trastuzumab 6mg/kg every 21 days to complete 1 year

Paclitaxel

Intervention Type: DRUG

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.

Doxorubicin

Intervention Type: DRUG

Doxorubicin 60 mg/m2 IV day 1

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide 600 mg/m2 IV day 1

Paclitaxel

Intervention Type: DRUG

80 mg/m2 IV x 1 hour infusion on days 1, 8, and 15

TCHP

TCHP (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.

Group Type: ACTIVE_COMPARATOR

Docetaxel

Intervention Type: DRUG

Docetaxel 75mg/m2 IV, day 1

Carboplatin

Intervention Type: DRUG

Carboplatin AUC 6 IV, day 1

Trastuzumab

Intervention Type: DRUG

Trastuzumab 8mg/kg IV initial dose, followed by 6mg/kg IV , day 1

Pertuzumab

Intervention Type: DRUG

Pertuzumab 840 mg IV initial dose followed by 420 mg IV, day 1

Pegfilgrastim

Intervention Type: DRUG

Pegfilgrastim 6mg SC, day 2 Cycled as per arm

Trastuzumab

Intervention Type: DRUG

Trastuzumab 6mg/kg every 21 days to complete 1 year

Paclitaxel

Intervention Type: DRUG

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.

Interventions

Docetaxel

Docetaxel 75mg/m2 IV, day 1

Intervention Type: DRUG

Carboplatin

Carboplatin AUC 6 IV, day 1

Intervention Type: DRUG

Trastuzumab

Trastuzumab 8mg/kg IV initial dose, followed by 6mg/kg IV , day 1

Intervention Type: DRUG

Pertuzumab

Pertuzumab 840 mg IV initial dose followed by 420 mg IV, day 1

Intervention Type: DRUG

Pegfilgrastim

Pegfilgrastim 6mg SC, day 2 Cycled as per arm

Intervention Type: DRUG

Trastuzumab

Trastuzumab 6mg/kg every 21 days to complete 1 year

Intervention Type: DRUG

Paclitaxel

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.

Intervention Type: DRUG

Doxorubicin

Doxorubicin 60 mg/m2 IV day 1

Intervention Type: DRUG

Cyclophosphamide

Cyclophosphamide 600 mg/m2 IV day 1

Intervention Type: DRUG

Paclitaxel

80 mg/m2 IV x 1 hour infusion on days 1, 8, and 15

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Aarti S. Bhardwaj

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Aarti Bhardwaj, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Mount Sinai Beth Israel

New York, New York, United States

Mount Sinai West

New York, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

GCO 17-1585

Identifier Type: -

Identifier Source: org_study_id