Carvedilol for the Prevention of Anthracycline/Anti-HER2 Therapy Associated Cardiotoxicity Among Women With HER2-Positive Breast Cancer Using Myocardial Strain Imaging for Early Risk Stratification

NCT02177175 | Completed Phase 2 Results

• 1 other identifier: 14-099
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to find out the effects, good and/or bad, of a beta blocker (carvedilol) on heart function during treatment with anti-HER2 medication(s) including trastuzumab (Herceptin).

Conditions

Breast Cancer

Keywords

Carvedilol; Anthracycline; HER2; 14-099

Outcome Measures

Primary Outcomes (4)

• Maximum Change in LVEF at 3 Months

  Value at 3 months minus value at baseline

  3 months

• Maximum Change in LVEF at 6 Months

  Value at 6 months minus value at baseline

  6 months

• Maximum Change in LVEF at 9 Months

  Value at 9 months minus value at baseline

  9 months

• Maximum Change in LVEF at 12 Months

  Value at 12 months minus value at baseline

  12 months

Secondary Outcomes (1)

• Incidence of Abnormal LVEF at 12 Months

  12 months

Study Arms (2)

Carvedilol

EXPERIMENTAL

Treatment in both carvedilol and placebo groups will be systematically up-titrated at weeks 3, 6, and 9 (+/- 1 week) after randomization to a goal dose of 25mg twice daily.

Drug: Carvedilol

placebo

PLACEBO COMPARATOR

Treatment in both carvedilol and placebo groups will be systematically up-titrated at weeks 3, 6, and 9 (+/- 1 week) after randomization to a goal dose of 25mg twice daily.

Other: placebo

Interventions

Carvedilol DRUG

Carvedilol

placebo OTHER

placebo

Eligibility Criteria

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

You may qualify if:

• Female
• Age ≥ 18 years
• Non-metastatic histologically confirmed primary invasive breast carcinoma
• Pathologically confirmed HER2-positive breast cancer
• Scheduled to receive anthracycline chemotherapy followed by anti-HER2 therapy at MSKCC
• Able and willing to provide informed consent
• Willing and able to comply with the requirements of the protocol
• Able to swallow capsules
• For Aim 2, all patients must meet the following criteria:
• LVEF \> 50%
• Abnormal global longitudinal strain (\<19%, or a % decrease of ≥ 11% from baseline) prior to initiation of planned anti-HER2 therapy
• Heart rate ≥ 50 beats per minute
• Sitting systolic blood pressure \> 90 mmHg

You may not qualify if:

• Patients are to be excluded from randomization for Aim 2 of this study if they meet any of the following criteria:
• Current treatment with ACE-inhibitors or beta blockers
• Allergies or inability to tolerate beta blockers previously due to bradycardia, hypotension, or AV block.
• Known history of NCI CTCAE (Version 4.0) Grade ≥ 2 symptomatic CHF, myocardial infarction within 12 months prior to randomization, significant symptoms (Grade ≥ 3) relating to left ventricular dysfunction, significant (moderate or severe) valvular disease, or significant cardiac arrhythmia (Grade ≥ 3)
• Pre-menopausal women without a negative serum or urine pregnancy test within 4 weeks of starting treatment
• Enrollment in a therapeutic intervention trial in the Breast Medicine service

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (2)

Memorial Sloan Kettering West Harrison

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Yu AF, Moore ZR, Moskowitz CS, Liu JE, Dang CT, Ramanathan L, Oeffinger KC, Steingart RM, Schmitt AM. Association of Circulating Cardiomyocyte Cell-Free DNA With Cancer Therapy-Related Cardiac Dysfunction in Patients Undergoing Treatment for ERBB2-Positive Breast Cancer. JAMA Cardiol. 2023 Jul 1;8(7):697-702. doi: 10.1001/jamacardio.2023.1229.

  PMID: 37256614 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Carvedilol

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Dr. Anthony Yu, MD
• Organization: Memorial Sloan Kettering Cancer Center

yua3@mskcc.org

212-639-7932

Study Officials

• Anthony Yu, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2014
• First Posted: June 27, 2014
• Study Start: June 24, 2014
• Primary Completion: June 24, 2021
• Study Completion: June 24, 2021
• Last Updated: July 12, 2022
• Results First Posted: July 12, 2022

Record last verified: 2021-06

Locations

US (2)