Risk-Guided Cardioprotection With Carvedilol in Breast Cancer Patients Treated With Doxorubicin and/or Trastuzumab

NCT ID: NCT04023110

Last Updated: 2025-10-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-09
• Study Completion Date: 2025-01-14

Brief Summary

Investigators will evaluate the safety, tolerability, and feasibility of a risk-guided cardioprotective treatment strategy with carvedilol, as compared to usual care, in breast cancer patients undergoing treatment with doxorubicin, trastuzumab, or the combination.

Detailed Description

This is a single-center, randomized clinical trial that seeks to determine if a risk guided treatment strategy that initiates carvedilol in high risk breast cancer patients prior to doxorubicin and/or trastuzumab is safe, tolerable, and feasible. Subjects who are identified as having elevated CTX Risk by an internally validated clinical risk score (exceeding a pre-specified risk threshold) will be randomized to individually-dosed, open-label carvedilol or usual care. Investigators will use a stratified randomization according to trastuzumab therapy (yes/no) to ensure balance across treatment regimen. Clinical, echocardiographic, and biomarker data will be collected on all patients at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months.

Conditions

Cardiotoxicity; Risk Factor, Cardiovascular; Toxicity Due to Chemotherapy; Breast Cancer; Cardiomyopathies; Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Carvedilol

Carvedilol will be initiated at 3.125mg twice daily and uptitrated as tolerated in a stepwise fashion to a maximum dose of 25mg twice daily or to a systolic blood pressure (SBP) of 110-120mmHg or heart rate (HR) of 50-55 beats per minute (bpm). Patients will start carvedilol in the evening after first dose of chemotherapy and will continue on medication for 12 months.

Clinical, echocardiographic, and biomarker data will be collected on all patients at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months.

Group Type: EXPERIMENTAL

Carvedilol

Intervention Type: DRUG

Individually dosed carvedilol

Usual Care

Clinical, echocardiographic, and biomarker data will be collected on all patients at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Carvedilol

Individually dosed carvedilol

Intervention Type: DRUG

Other Intervention Names

Coreg

Eligibility Criteria

Inclusion Criteria

• Females
• At least 18 years old
• Diagnosed with Stage I-III breast cancer with treatment plan to include therapy with anthracyclines and/or trastuzumab in the adjuvant or neo-adjuvant setting
• Study team is able to obtain all necessary information for calculating Cardiotoxicity Risk Score (including echocardiographic measurement of left ventricular ejection fraction)

Exclusion Criteria

• Pregnant or breast feeding. Due to unknown risks and potential harm to the unborn fetus a negative pregnancy test within 10 days prior to enrollment is required in women with child-bearing potential. Due to the potential nursing infant harm, women who are currently breast feeding are not eligible for this study.
• Contraindication to carvedilol
• Baseline systolic blood pressure < 90mmHg (if multiple blood pressures are available in the medical record within 1 month prior to screening, the average SBP will be considered)
• Baseline heart rate < 55 bpm consistent with severe bradycardia (if multiple resting heart rates are available in the medical record within 1 month prior to screening, the average heart rate will be considered)
• Allergy to carvedilol
• History of bronchial asthma or related bronchospastic conditions
• Known history of sick sinus syndrome
• Severe hepatic impairment, defined as serum bilirubin > 3.0x ULN, AST or ALT > 5.0 ULN within 28 days of enrollment
• Second- or third-degree AV block, as determined by electrocardiogram
• Severe bradycardia (unless permanent pacemaker is in place)
• Patients in cardiogenic shock or decompensated heart failure requiring the use of IV inotropic therapy
• Current use of: Bupropion (Wellbutrin), Fluoxetine (Prozac), Paroxetine (Paxil), Quinidine (Quinidex), Duloxetine (Cymbalta), Digoxin
• Current treatment with beta blocker
• Unable to provide consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

American Heart Association

OTHER

Sponsor Role: collaborator

Abramson Cancer Center at Penn Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bonnie Ky, MD, MSCE

Role: PRINCIPAL_INVESTIGATOR

Perelman School of Medicine at the University of Pennsylvania

Locations

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

Jung W, Hubbard RA, Smith AM, Ko K, Huang A, Wang J, Isaacs JM, Zhang L, Liu PP, Chen Z, Shah PD, Mintzer D, Bhattacharya S, Knollman HM, Clark AS, Koropeckyj-Cox D, Messinger M, Wilcox NS, Xia C, Narayan V, Upshaw JN, Armenian SH, Ky B. Risk-guided cardioprotection with carvedilol in patients with breast cancer (CCT guide): a phase 1 randomized clinical trial. Breast Cancer Res Treat. 2025 Jun;211(2):293-305. doi: 10.1007/s10549-025-07636-3. Epub 2025 Apr 2.

Reference Type: DERIVED

PMID: 40172740 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R21HL150723

Identifier Type: NIH

Identifier Source: secondary_id

View Link

849569

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

UPCC12118

Identifier Type: -

Identifier Source: org_study_id