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

NCT ID: NCT06844669

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-16
• Study Completion Date: 2026-05-31

Brief Summary

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.

Conditions

HER2-positive Breast Cancer; HER2+ Breast Cancer

Keywords

Breast cancer; Cardiotoxicity; Heart failure; Cardio-oncology

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Arm 1: Carvedilol BID

Carvedilol by mouth twice per day (BID) for 12 weeks.

Group Type: EXPERIMENTAL

Carvedilol

Intervention Type: DRUG

6.25 mg with food

Arm 2: Empagliflozin QD

Empagliflozin by mouth daily (QD) for 12 weeks.

Group Type: EXPERIMENTAL

Empagliflozin

Intervention Type: DRUG

10 mg in the morning with or without food

Arm 3: Carvedilol BID + Empagliflozin QD

Carvedilol by mouth twice per day (BID) for 12 weeks and empagliflozin by mouth daily (QD) for 12 weeks.

Group Type: EXPERIMENTAL

Carvedilol

Intervention Type: DRUG

6.25 mg with food

Empagliflozin

Intervention Type: DRUG

10 mg in the morning with or without food

Arm 4: Usual Care

No medications.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Carvedilol

6.25 mg with food

Intervention Type: DRUG

Empagliflozin

10 mg in the morning with or without food

Intervention Type: DRUG

Other Intervention Names

Coreg; Jardiance

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed HER2+ breast cancer by ASCO/CAP guidelines of any clinical or pathologic stage.
• Planning to commence standard of care HER2-directed therapy or started HER2-directed therapy within 6 months prior to randomization
• At least 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• For patients newly commencing HER2-directed therapy, left ventricular ejection fraction (LVEF) ≥ 50% up to 30 days prior to enrollment detected by echocardiogram. For patients already receiving HER2-directed therapy, LVEF ≥ 50% after the last cycle of therapy prior to enrollment. (Patient will be enrolled at the time of their next cycle after the echocardiogram.)
• 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.

Exclusion Criteria

• 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 as determined by the treating physician. 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 requiring central nervous system directed therapy and interruption of systemic HER2 directed therapy (as determined by the treating medical team.
• A known 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
• 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 14 days of study entry.

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

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

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

Role: CONTACT

Phone: 314-494-3124

Email: jdmitchell@wustl.edu

Sang Gune Yoo, M.D.

Role: CONTACT

Phone: 314-901-2455

Email: skyoo@wustl.edu

Facility Contacts

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

Role: primary

Sang Gune Yoo, M.D.

Role: backup

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

202502113

Identifier Type: -

Identifier Source: org_study_id