RECRUITING

HER2HEART-US: Prevention of Cardiotoxicity in Breast Cancer Patients Receiving HER2-directed Therapy

Conditions

HER2-positive Breast Cancer HER2+ Breast Cancer Breast cancer Cardiotoxicity Heart failure Cardio-oncology

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Ten to 15% of patients with breast cancer are HER2 positive, with treatment focused on targeting the HER2 receptor. Although these treatments are generally well tolerated, they are associated with an increased risk of cardiomyopathy. There are currently no treatments proven to prevent the cardiotoxicities associated with HER2-targeted therapy, but there is convincing preclinical data demonstrating that prophylactic treatment with a beta blocker (BB) and/or an SGLT2 inhibitor (SGLT2i) may each independently prevent cardiotoxicity and HER-targeted treatment interruptions. The proposed pilot study will assess the feasibility and preliminary efficacy and safety of therapy with both a beta blocker (carvedilol) and an SGLT2 inhibitor (empagliflozin), alone and in combination, in a population initiating HER2-directed therapy for HER2+ breast cancer. The hypotheses being tested in this study are: 1. It is feasible to recruit 20-40 patients over 6 months 2. There are no differences in tolerability and safety between participants taking carvedilol and/or empagliflozin and those receiving usual care.

Official Title

HER2HEART-US: Primary Prevention of Cardiotoxicity in Breast Cancer Patients Receiving HER2-directed Therapy: a Pilot 2x2 Factorial Randomized Controlled Trial

Quick Facts

Study Start:2025-04-16

Study Completion:2026-01-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06844669

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histologically or cytologically confirmed HER2+ breast cancer of any stage. * Planning to commence standard of care HER2-directed therapy. * At least 18 years of age. * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Left ventricular ejection fraction (LVEF) ≥ 50% up to 30 days prior to enrollment detected by any imaging modality. * Systolic blood pressure ≥ 100 mmHg and resting heart rate ≥ 60 bpm. * eGFR \> 30 mL/min/1.73m\^2. * Women of childbearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Patients with an acceptable support system (as determined by the treating medical team). * Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.	* Prior exposure to mantle cell lymphoma field radiation. * Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial. * Currently receiving treatment with SGLT2i or BB that cannot be stopped during the duration of study participation. Currently receiving non-dihydropyridine calcium channel blocker that cannot be transitioned to or used in combination with carvedilol. * Patients with untreated brain metastases. Patients with treated brain metastases are allowed if post-treatment brain-imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to carvedilol, empagliflozin, or other agents used in the study. * Contraindication to carvedilol or empagliflozin at the discretion of the investigator such as: * Bronchial asthma or related bronchospastic conditions where BB would be contraindicated * Second- or third-degree atrioventricular (AV) block * Sick sinus syndrome * Severe bradycardia (unless permanent pacemaker in place) * In cardiogenic shock or decompensated heart failure requiring the use of IV inotropic therapy * Severe hepatic impairment in setting of cirrhosis that prevents use of carvedilol * Prior breast cancer treatment with anthracyclines or HER2 antagonists. * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection or uncontrolled cardiac arrhythmia. * Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.

Inclusion Criteria

Exclusion Criteria

* Histologically or cytologically confirmed HER2+ breast cancer of any stage.
* Planning to commence standard of care HER2-directed therapy.
* At least 18 years of age.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Left ventricular ejection fraction (LVEF) ≥ 50% up to 30 days prior to enrollment detected by any imaging modality.
* Systolic blood pressure ≥ 100 mmHg and resting heart rate ≥ 60 bpm.
* eGFR \> 30 mL/min/1.73m\^2.
* Women of childbearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
* Patients with an acceptable support system (as determined by the treating medical team).
* Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

* Prior exposure to mantle cell lymphoma field radiation.
* Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
* Currently receiving treatment with SGLT2i or BB that cannot be stopped during the duration of study participation. Currently receiving non-dihydropyridine calcium channel blocker that cannot be transitioned to or used in combination with carvedilol.
* Patients with untreated brain metastases. Patients with treated brain metastases are allowed if post-treatment brain-imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to carvedilol, empagliflozin, or other agents used in the study.
* Contraindication to carvedilol or empagliflozin at the discretion of the investigator such as:
* Bronchial asthma or related bronchospastic conditions where BB would be contraindicated
* Second- or third-degree atrioventricular (AV) block
* Sick sinus syndrome
* Severe bradycardia (unless permanent pacemaker in place)
* In cardiogenic shock or decompensated heart failure requiring the use of IV inotropic therapy
* Severe hepatic impairment in setting of cirrhosis that prevents use of carvedilol
* Prior breast cancer treatment with anthracyclines or HER2 antagonists.
* Uncontrolled intercurrent illness including, but not limited to ongoing or active infection or uncontrolled cardiac arrhythmia.
* Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.

Contacts and Locations

Study Contact

Joshua Mitchell, M.D., MSCI, FAC, FICOS

CONTACT

314-494-3124

jdmitchell@wustl.edu

Sang Gune Yoo, M.D.

CONTACT

314-901-2455

skyoo@wustl.edu

Principal Investigator

Joshua Mitchell, M.D., MSCI, FAC, FICOS

PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Study Locations (Sites)

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

Collaborators and Investigators

Sponsor: Washington University School of Medicine

Joshua Mitchell, M.D., MSCI, FAC, FICOS, PRINCIPAL_INVESTIGATOR, Washington University School of Medicine

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 Registration Dates

Study Start Date2025-04-16

Study Completion Date2026-01-31

Study Record Updates

Study Start Date2025-04-16

Study Completion Date2026-01-31

Terms related to this study

Keywords Provided by Researchers

Breast cancer
Cardiotoxicity
Heart failure
Cardio-oncology

Additional Relevant MeSH Terms

HER2-positive Breast Cancer
HER2+ Breast Cancer