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

July 11, 2022 updated by: Memorial Sloan Kettering Cancer Center
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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

82

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Harrison, New York, United States, 10604
        • Memorial Sloan Kettering West Harrison
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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:

  • Meet all inclusion criteria above

    • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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.
Drug: Carvedilol
PLACEBO_COMPARATOR: 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.
Other: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Change in LVEF at 3 Months
Time Frame: 3 months
Value at 3 months minus value at baseline
3 months
Maximum Change in LVEF at 6 Months
Time Frame: 6 months
Value at 6 months minus value at baseline
6 months
Maximum Change in LVEF at 9 Months
Time Frame: 9 months
Value at 9 months minus value at baseline
9 months
Maximum Change in LVEF at 12 Months
Time Frame: 12 months
Value at 12 months minus value at baseline
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Abnormal LVEF at 12 Months
Time Frame: 12 months
The study is designed to detect an intergroup difference of absolute difference of 10 percentage points (simple difference) in the change in LVEF between the experimental and control group. Ten percent is the change in LVEF that is associated with differing degrees of left ventricular dysfunction, and long-term studies among non-cancer patients have shown that outcomes differ among groups of patients who have LVEF differing by 10%.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 24, 2014

Primary Completion (ACTUAL)

June 24, 2021

Study Completion (ACTUAL)

June 24, 2021

Study Registration Dates

First Submitted

June 26, 2014

First Submitted That Met QC Criteria

June 26, 2014

First Posted (ESTIMATE)

June 27, 2014

Study Record Updates

Last Update Posted (ACTUAL)

July 12, 2022

Last Update Submitted That Met QC Criteria

July 11, 2022

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14-099

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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