HER2-positive Breast CancerPhase 2NCT06844669
HER2HEART-US: Prevention of Cardiotoxicity in Breast Cancer Patients Receiving HER2-directed Therapy
A Phase 2 study testing Carvedilol and Empagliflozin in people with HER2-positive Breast Cancer and HER2+ Breast Cancer, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-positive Breast Cancer, HER2+ Breast Cancer
- What is being tested?
- Carvedilol and Empagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Apr 2025to 7 May 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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:
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: HER2HEART-US: Primary Prevention of Cardiotoxicity in Breast Cancer Patients Receiving HER2-directed Therapy: a Pilot 2x2 Factorial Randomized Controlled Trial
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.
Read more
The hypotheses being tested in this study are:
- It is feasible to recruit 20-40 patients over 6 months
- 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
- Being tested
- Carvedilol, Empagliflozin
- Keywords
- Breast cancer, Cardiotoxicity, Heart failure, Cardio-oncology
- Medical subject headings
- Breast Neoplasms, Cardiotoxicity, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
Also called Coreg
6.25 mg with food
EmpagliflozinDrug
Also called Jardiance
10 mg in the morning with or without food
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Carvedilol BID | Experimental | Carvedilol by mouth twice per day (BID) for 12 weeks. Receives: Drug: Carvedilol |
| Arm 2: Empagliflozin QD | Experimental | Empagliflozin by mouth daily (QD) for 12 weeks. Receives: Drug: Empagliflozin |
| Arm 3: Carvedilol BID + Empagliflozin QD | Experimental | Carvedilol by mouth twice per day (BID) for 12 weeks and empagliflozin by mouth daily (QD) for 12 weeks. Receives: Drug: Carvedilol; Drug: Empagliflozin |
| Arm 4: Usual Care | No intervention | No medications. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of HER2HEART as measured by the number of patients enrolled over a 10-month period
Feasibility is defined as enrollment of 20-40 patients (5-10 per am) over a 10-month recruitment period.
Measured: 10 months
Secondary outcomes (4)
Tolerability as measured by treatment adherence via self-report
Measured: From start of treatment through last day of study treatment (estimated to be 3 months)
Tolerability as measured by incidence of serious adverse events
Measured: From start of treatment through last day of study treatment (estimated to be 3 months)
Tolerability as measured by incidence of adverse events of special interest
- Symptomatic hypotension (systolic blood pressure <90 mmHg)
- Symptomatic bradycardia (heart rate <50 bpm)
- Acute renal dysfunction (eGFR decrease >30% from baseline)
- Syncope
- Symptomatic hypoglycemia (blood glucose <70 mg/dL)
- Perineal infection
- Urinary tract infection
- Diabetic ketoacidosis (commonly accepted criteria are blood glucose > 250 mg/dL, arterial pH < 7.3, serum bicarbonate < 15 mEq/L, and the presence of ketonemia or ketonuria).
- Euglycemic diabetic ketoacidosis (diabetic ketoacidosis in the absence of hyperglycemia)
Measured: From start of treatment through last day of study treatment (estimated to be 3 months)
Tolerability as measured by number of participants who withdraw from the study due to adverse events
Measured: From start of treatment through last day of study treatment (estimated to be 3 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2025
- Study start16 Apr 2025
- Primary completion16 Feb 2026
- Study completion7 May 2026
Why it stopped: Futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-positive Breast CancerStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- This is a 2x2 factorial, open-label, randomized pilot study. Patients will be randomized on a 1:1 basis to either carvedilol or no carvedilol, and again on a 1:1 basis to either empagliflozin or no empagliflozin, meaning that there are four arms: * Arm 1: carvedilol * Arm 2: empagliflozin * Arm 3: carvedilol + empagliflozin * Arm 4: usual care
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joshua Mitchell, M.D., MSCI, FAC, FICOS, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06844669
- Sponsor's protocol ID
- 202502113
- Status last verified
- May 2026
- First submitted
- 17 Feb 2025
- Last updated
- 13 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial will be shared after deidentification. These requests are reviewed and will be approved by study investigators on the basis of scientific merit.
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HER2HEART-US: Primary Prevention of Cardiotoxicity in Breast Cancer Patients Receiving HER2-directed Therapy: a Pilot 2x2 Factorial Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06844669
- Acronym / sponsor ID
- 202502113
- Conditions
- HER2-positive Breast Cancer, HER2+ Breast Cancer
- Keywords
- Breast cancer, Cardiotoxicity, Heart failure, Cardio-oncology
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Futility
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 16 Apr 2025 (actual)
- Primary completion
- 16 Feb 2026 (actual)
- Study completion
- 7 May 2026 (actual)
- First posted
- 25 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- It is feasible to recruit 20-40 patients over 6 months
- There are no differences in tolerability and safety between participants taking carvedilol and/or empagliflozin and those receiving usual care.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- This is a 2x2 factorial, open-label, randomized pilot study. Patients will be randomized on a 1:1 basis to either carvedilol or no carvedilol, and again on a 1:1 basis to either empagliflozin or no empagliflozin, meaning that there are four arms: * Arm 1: carvedilol * Arm 2: empagliflozin * Arm 3: carvedilol + empagliflozin * Arm 4: usual care
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Carvedilol BID | Experimental | Drug: CarvedilolCarvedilol by mouth twice per day (BID) for 12 weeks. |
| Arm 2: Empagliflozin QD | Experimental | Drug: EmpagliflozinEmpagliflozin by mouth daily (QD) for 12 weeks. |
| Arm 3: Carvedilol BID + Empagliflozin QD | Experimental | Drug: Carvedilol, Drug: EmpagliflozinCarvedilol by mouth twice per day (BID) for 12 weeks and empagliflozin by mouth daily (QD) for 12 weeks. |
| Arm 4: Usual Care | No intervention | –No medications. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.)
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarvedilolAlso: Coreg6.25 mg with food | Drug | Arm 1: Carvedilol BID, Arm 3: Carvedilol BID + Empagliflozin QD |
| EmpagliflozinAlso: Jardiance10 mg in the morning with or without food | Drug | Arm 2: Empagliflozin QD, Arm 3: Carvedilol BID + Empagliflozin QD |
Primary outcome
Feasibility of HER2HEART as measured by the number of patients enrolled over a 10-month period
Time frame: 10 months
Feasibility is defined as enrollment of 20-40 patients (5-10 per am) over a 10-month recruitment period.
4 secondary outcomes
Tolerability as measured by treatment adherence via self-report
Time frame: From start of treatment through last day of study treatment (estimated to be 3 months)
Tolerability as measured by incidence of serious adverse events
Time frame: From start of treatment through last day of study treatment (estimated to be 3 months)
Tolerability as measured by incidence of adverse events of special interest
Time frame: From start of treatment through last day of study treatment (estimated to be 3 months)
Tolerability as measured by number of participants who withdraw from the study due to adverse events
Time frame: From start of treatment through last day of study treatment (estimated to be 3 months)
Results and safety
The study was stopped early (reason given: Futility). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial will be shared after deidentification. These requests are reviewed and will be approved by study investigators on the basis of scientific merit.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joshua Mitchell, M.D., MSCI, FAC, FICOS principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carvedilol and Empagliflozin in people with HER2-positive Breast Cancer and HER2+ Breast Cancer, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Futility). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of HER2HEART as measured by the number of patients enrolled over a 10-month period (time frame: 10 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2026.