Treating Breast Cancer Patients Undergoing Trastuzumab Treatment With Carvedilol to Reduce Incidence of Heart Failure

NCT03879629 | Active Not Recruiting Phase 2 FDA Drug

• 5 other identifiers: TACTICR01CA233610NCI-2019-08427MC193218-006090
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Rate of asymptomatic and symptomatic cardiac dysfunction

  Incidence of heart failure or asymptomatic decline in left-ventricular ejection fraction (LVEF) by \>10% in patients whose LVEF is ≥50% or LVEF drop ≥5% in those with a decrease to \<50% (primary outcome measure)

  1 year

• Rate of reversible cardiac function decline

  Reversible LVEF decline to within 5% of baseline (secondary primary outcome measure)

  1 year

Secondary Outcomes (2)

• Cardiac function changes after completion of HER2-directed therapy

  1 year

• Gene variants and risk of cardiotoxicity and response to therapy

  2 years

Study Arms (3)

Pre-Emptive Strategy

EXPERIMENTAL

Carvedilol titrated to maximally tolerated doses (3.125 mg to 25 mg twice a day) initiated one week before start of therapy and continued until end of therapy

Drug: Carvedilol

Reactive Strategy

EXPERIMENTAL

Carvedilol titrated to maximally tolerated doses (3.125 mg to 25 mg twice a day) initiated after documentation of subclinical cardiotoxicity, defined by an abnormal global longitudinal strain (GLS) or high-sensitive cardiac troponin (hsTnI) elevation and continued until end of therapy

Drug: Carvedilol

Standard of Care

ACTIVE COMPARATOR

Carvedilol titrated to maximally tolerated doses (3.125 mg to 25 mg twice a day) initiated after documentation of a drop in LVEF by \>10% to a value less than 53% and continued until end of therapy

Drug: Carvedilol

Interventions

Carvedilol DRUG

oral Carvedilol maximally tolerated doses 3.125 mg to 25 mg twice a day

Also known as: Coreg

Pre-Emptive Strategy; Reactive Strategy; Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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".

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator
• Miami Heart Research Institute: collaborator

Study Sites (5)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Carvedilol

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Study Officials

• Joerg Herrmann, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2019
• First Posted: March 19, 2019
• Study Start: August 21, 2019
• Primary Completion: February 28, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: November 20, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)