Using carvedilol to protect breast cancer patients from heart failure during trastuzumab treatment

TrAstuzumab Cardiomyopathy Therapeutic Intervention with Carvedilol (TACTIC) Trial

This study is testing if the heart medication carvedilol can help protect breast cancer patients from heart failure while they are being treated with trastuzumab.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 450 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Mayo Clinic (other)
• Drugs / interventions: Trastuzumab, pertuzumab, Nerantinib, lapatinib
• Locations: 5 sites (Phoenix, Arizona and 4 other locations)
• Trial ID: NCT03879629 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of carvedilol, a beta-blocker, in reducing the risk of heart failure in breast cancer patients receiving trastuzumab-based HER2-directed therapy. Participants will be randomly assigned to receive carvedilol either preventively before starting treatment or reactively in response to early signs of heart injury. The study aims to determine the optimal timing and duration of carvedilol therapy to protect heart function. Additionally, pharmacogenomic measures will be used to identify patients at higher risk of heart function decline.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a new or locally recurrent diagnosis of HER2+ breast cancer planned for curative treatment.

Not a fit: Patients with a history of heart failure, low left ventricular ejection fraction, or those intolerant to beta-blockers may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the incidence of heart failure in breast cancer patients undergoing trastuzumab treatment.

How similar studies have performed: Previous studies have shown promise in using beta-blockers for cardioprotection in cancer patients, but this specific approach is novel.

Eligibility criteria

Inclusion Criteria:

* ≥18 years of age,
* new or locally recurrent diagnosis of HER2+ breast cancer that will be treated with curative intent
* planned HER2-directed (any therapy targeting HER2 signaling including Trastuzumab +/- pertuzumab or trastuzumab-emtansine (T-DM1) Nerantinib and lapatinib will not be considered. "HER2-directed therapy" or "anti-HER-2".

Exclusion Criteria:

* history of HF of any class and type, or diagnosis of cardiomyopathy in the past,
* LVEF \<50% at screening,
* intolerance to beta-blocker,
* baseline use of any beta-blocker for coronary artery disease including myocardial infarction
* current ACE inhibitor or ARB therapy for hypertension in the presence of diabetes and/or for chronic kidney disease/proteinuria,
* on active therapy with amiodarone, sotalol, or any other antiarrhythmic
* Diagnosis of asthma with current daily use of anti-asthmatic therapy
* heart rate \< 50 BPM at screening (average of 3 most recent readings)
* history of or current sick sinus syndrome,
* AV block grade II or higher (unless patient has a permanent pacemaker) at screening,
* systolic blood pressure \< 90 mmHg at screening (average of 3 most recent readings)
* severe hepatic dysfunction, as defined by NCI ODWG (total bilirubin \>3x ULN, any AST elevation) or Child Pugh C class
* pregnancy
* Metastatic breast cancer (distant metastases)
* Active systemic treatment for non-breast cancer

Where this trial is running

Phoenix, Arizona and 4 other locations

• Mayo Clinic — Phoenix, Arizona, United States (ACTIVE_NOT_RECRUITING)
• Mayo Clinic in Florida — Jacksonville, Florida, United States (RECRUITING)
• Mayo Clinic in Rochester — Rochester, Minnesota, United States (RECRUITING)
• Washington University in St. Louis — Saint Louis, Missouri, United States (RECRUITING)
• MD Anderson Cancer Center — Houston, Texas, United States (RECRUITING)

Study contacts

• Principal investigator: Joerg Herrmann, MD — Mayo Clinic
• Study coordinator: Monica Olson

Conditions: Breast Cancer