TrAstuzumab Cardiomyopathy Therapeutic Intervention With Carvedilol

• Status: Recruiting
• Trial end date: 2025-09-30
• Target enrollment: 0
• Participant gender: All

Summary

Breast cancer patients undergoing trastuzumab-based HER2-directed therapy are at risk of heart function decline or heart failure symptoms, but it is unknown if, when, and for how long cardiovascular protective strategies, e.g. with a beta-blocker, could help. This study randomly assigns those taking curative-intent trastuzumab-based HER2-directed therapy to the beta-blocker carvedilol-either when significant heart function decline or subtle early signs of heart injury (either by elevation of a cardiac blood biomarker, i.e. cardiac troponin, or by an abnormal heart ultrasound marker, i.e. global longitudinal strain) are noted, or preventatively before beginning trastuzumab-based HER2-directed therapy. This study will further randomly assign those patients on carvedilol to either discontinuation at the end of trastuzumab-based HER2-directed therapy or continuation for another year, providing much needed clinical trial data on what the best strategy ("tactic") for those at risk of cardiotoxicity with trastuzumab-based HER2-directed therapy is.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mayo Clinic
• Collaborator: National Cancer Institute (NCI)
• Treatments: Carvedilol; Trastuzumab

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