TrAstuzumab Cardiomyopathy Therapeutic Intervention With Carvedilol
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.
Conditions:
🦠 Breast Cancer
🗓️ Study Start (Actual) 21 August 2019
🗓️ Primary Completion (Estimated) 28 February 2028
✅ Study Completion (Estimated) 28 February 2029
👥 Enrollment (Estimated) 450
🔬 Study Type INTERVENTIONAL
📊 Phase PHASE2
Locations:
📍 Phoenix, Arizona, United States
📍 Jacksonville, Florida, United States
📍 Rochester, Minnesota, United States
📍 Saint Louis, Missouri, United States
📍 Houston, Texas, United States

📋 Eligibility Criteria

Description

    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
Ages Eligible for Study: 18 Years to N/A (ADULT, OLDER_ADULT)
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers: No

🗓️ Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

  • First Submitted 8 March 2019
  • First Submitted that Met QC Criteria 14 March 2019
  • First Posted 19 March 2019

Study Record Updates

  • Last Update Submitted that Met QC Criteria 25 January 2024
  • Last Update Posted 29 January 2024
  • Last Verified January 2024