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

NCT ID: NCT02177175

Last Updated: 2022-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-24
• Study Completion Date: 2021-06-24

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).

Detailed Description

This phase II placebo-controlled study will evaluate the effect of carvedilol, compared to placebo, on anthracycline/anti-HER2 therapy induced left ventricular dysfunction in patients with HER2-positive breast cancer who are receiving adjuvant or neoadjuvant therapy. All patients will undergo routine cardiac surveillance with 2D echocardiograms per standard of care at multiple time points which will align as closely as possible to the following: pre-anthracycline (baseline), pre-anti-HER2 therapy, and 3, 6, 9, and 12 months (+/- 4 weeks) after initiation of anti-HER2 therapy. In the case that standard of care echocardiograms are not done at these time points, either due to a delay in anti-cancer therapy or due to the patient's medical condition, the principal investigator will determine if the standard of care echocardiogram may be used in lieu of one of the time points listed. Additional speckle tracking strain analysis will be performed on these echocardiograms, and blood specimens will be drawn at several time points for biomarker analysis.

After completion of anthracycline treatment and prior to initiation of anti-HER2 therapy, 32 patients with abnormal myocardial strain, defined as global longitudinal strain < 19% or % change from baseline by > 11%, will be randomized in a 1:1 ratio to carvedilol versus placebo. Carvedilol will be administered twice daily for approximately 1 year OR until the end of anti-HER2 therapy, if it is discontinued prior to 1 year. 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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Carvedilol

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.

Group Type: EXPERIMENTAL

Carvedilol

Intervention Type: DRUG

placebo

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.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Interventions

Carvedilol

Intervention Type: DRUG

placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

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

Sponsors

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anthony Yu, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering West Harrison

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37256614 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.mskcc.org/

Memorial Sloan Kettering Cancer Center

Other Identifiers

14-099

Identifier Type: -

Identifier Source: org_study_id