Skip to main content

Carvedilol in Reducing the Risk of Cardiotoxicity in Patients with Stage I-III Breast Cancer Treated with Doxorubicin and / or Trastuzumab

Trial Status: Active

This phase I trial studies the side effects and best dose of carvedilol in reducing the risk of cardiotoxicity in patients with stage I-III breast cancer who are being treated with doxorubicin and / or trastuzumab. Some cancer treatments can cause damage to the heart. A risk calculator has been developed to predict the likelihood that this damage (called cardiotoxicity) will be experienced. This study is being conducted to test whether this calculator can be used to identify patients who may benefit from medicines to protect the heart and to test whether a medicine, called carvedilol, can be used to protect the heart during chemotherapy for patients who are identified as being at elevated risk.

Inclusion Criteria

  • Diagnosed with stage I-III breast cancer, with treatment plan to include therapy with anthracyclines and/or trastuzumab in the adjuvant or neoadjuvant setting
  • Able to swallow tablets
  • Study team is able to obtain all necessary information for calculating baseline CTX risk (including echocardiographic images for quantitation of left ventricular ejection fraction [LVEF]) prior to enrollment
  • Standard of care pre-chemotherapy measurement of LVEF by echocardiogram (patients with pre-chemo multigated acquisition scan [MUGA] will be asked to come in for a research echocardiogram as part of screening)

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 < 90 mmHg (if multiple blood pressures are available in the medical record within 1 month prior to screening, the average systolic blood pressure [SBP] will be considered) * Baseline heart rate < 55 beats per minute (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 > 3.0 x upper limit of normal (ULN), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5.0 ULN within 28 days of enrollment * Second- or third-degree atrioventricular (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 intravenous (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

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: ACTIVE
Contact: Bonnie Ky
Phone: 215-573-6606

PRIMARY OBJECTIVES:

I. To determine feasibility and safety/tolerability.

SECONDARY OBJECTIVES:

I. To prospectively validate our cardiotoxicity (CTX) risk score.

II. To explore the impact of a risk-guided cardioprotective treatment strategy with carvedilol, as compared to usual care, on measures of cardiovascular (CV) function and stress, derived from echocardiography and blood biomarkers, and on clinical heart failure.

OUTLINE: This is a dose-escalation study. Patients are randomized to 1 of 2 arms.

ARM I: Beginning day 1 of standard of care chemotherapy, patients receive carvedilol orally (PO) twice daily (BID) for 12 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive usual care.

After completion of study, patients are followed up at 30 days (carvedilol arm only) and 24 months.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
University of Pennsylvania / Abramson Cancer Center

Principal Investigator
Bonnie Ky

  • Primary ID UPCC 12118
  • Secondary IDs NCI-2019-05301
  • Clinicaltrials.gov ID NCT04023110