Neoadjuvant Dose-Dense For Early Her2Neu Positive Breast Cancer

NCT03329378 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: GCO 17-1585
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 3

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

Keywords

Neoadjuvant chemotherapy; locally advanced breast cancer; Her2neu

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Pathologic Complete Response (pCR)

  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.

  2 years

Secondary Outcomes (4)

• Number of Cardiac Toxicity Events

  2 years

• Number of Non-cardiac Toxicities

  2 years

• Number of Participants With Breast Conservation

  2 years

• Number of Participants Alive at the End of the Study

  2 years

Study Arms (2)

ddACTHP

ACTIVE COMPARATOR

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

Drug: Pertuzumab; Drug: Trastuzumab; Drug: Paclitaxel; Drug: Doxorubicin; Drug: Cyclophosphamide

TCHP

ACTIVE COMPARATOR

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.

Drug: Docetaxel; Drug: Carboplatin; Drug: Trastuzumab; Drug: Pertuzumab; Drug: Pegfilgrastim; Drug: Paclitaxel

Interventions

Docetaxel DRUG

Docetaxel 75mg/m2 IV, day 1

TCHP

Carboplatin DRUG

Carboplatin AUC 6 IV, day 1

TCHP

Trastuzumab DRUG

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

TCHP

Pertuzumab DRUG

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

TCHP; ddACTHP

Pegfilgrastim DRUG

Pegfilgrastim 6mg SC, day 2 Cycled as per arm

TCHP

Paclitaxel 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.

TCHP; ddACTHP

Doxorubicin DRUG

Doxorubicin 60 mg/m2 IV day 1

ddACTHP

Cyclophosphamide DRUG

Cyclophosphamide 600 mg/m2 IV day 1

ddACTHP

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient must have signed and dated an IRB-approved consent form that conforms to federal and institutional guidelines.
• Female
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (3)

Mount Sinai Beth Israel

New York, New York, 10011, United States

Location

Mount Sinai West

New York, New York, 10019, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Interventions

Docetaxel; Carboplatin; Trastuzumab; pertuzumab; pegfilgrastim; Paclitaxel; Doxorubicin; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Aarti Bhardwaj
• Organization: Icahn School of Medicine at Mount Sinai

Aarti.Bhardwaj@mountsinai.org

(212) 824-8578

Study Officials

• Aarti Bhardwaj, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: November 6, 2017
• Study Start: January 24, 2019
• Primary Completion: March 7, 2021
• Study Completion: March 7, 2021
• Last Updated: August 22, 2023
• Results First Posted: August 22, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)