Preventing heart damage in breast cancer patients receiving HER2 therapy
HER2HEART-US: Primary Prevention of Cardiotoxicity in Breast Cancer Patients Receiving HER2-directed Therapy: a Pilot 2x2 Factorial Randomized Controlled Trial
This study is testing whether a heart medication and a diabetes drug can help prevent heart damage in breast cancer patients starting HER2 therapy.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 40 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Washington University School of Medicine Academic / other |
| Drugs / interventions | radiation |
| Locations | 1 site (Saint Louis, Missouri) |
| Trial ID | NCT06844669 on ClinicalTrials.gov |
What this trial studies
This pilot study aims to evaluate the feasibility and preliminary efficacy of using a beta blocker (carvedilol) and an SGLT2 inhibitor (empagliflozin) to prevent cardiotoxicity in patients starting HER2-directed therapy for HER2-positive breast cancer. The study will recruit 20-40 patients over six months and assess the safety and tolerability of these treatments, both individually and in combination. The goal is to determine if these medications can help mitigate the risk of heart complications associated with HER2-targeted therapies.
Who should consider this trial
Good fit: Ideal candidates include women aged 18 and older with histologically confirmed HER2-positive breast cancer who are about to start HER2-directed therapy.
Not a fit: Patients who are concurrently receiving anthracycline therapy or have a left ventricular ejection fraction below 50% may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly reduce the risk of heart damage in breast cancer patients undergoing HER2-directed therapy.
How similar studies have performed: While there is promising preclinical data supporting the use of beta blockers and SGLT2 inhibitors for this purpose, this specific approach is novel and has not been extensively tested in clinical settings.
Eligibility criteria
Show full inclusion / exclusion 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. Plan for concurrent anthracycline with HER2-directed therapy is exclusionary. * 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 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 * Prior cancer treatment with anthracyclines. * 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.
Where this trial is running
Saint Louis, Missouri
- Washington University School of Medicine — Saint Louis, Missouri, United States (Recruiting)
Study contacts
- Principal investigator: Joshua Mitchell, M.D., MSCI, FAC, FICOS — Washington University School of Medicine
- Study coordinator: Joshua Mitchell, M.D., MSCI, FAC, FICOS
- Email: jdmitchell@wustl.edu
- Phone: 314-494-3124
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.