Clinical trial NCT04023110: Risk-Guided Cardioprotection with Carvedilol in Breast Cancer Patients Treated with Doxorubicin And/or Trastuzumab
Official title: A Pilot Study of Risk-Guided Cardioprotection with Carvedilol in Breast Cancer Patients Treated with Doxorubicin And/or Trastuzumab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cardiotoxicity
Risk Factor, Cardiovascular
Toxicity Due to Chemotherapy
Breast Cancer
Cardiomyopathies
Heart Failure
Keywords: Risk-Guided Intervention
Carvedilol
Cardiotoxicity of Chemotherapy
Cardio-Oncology
Cardiomyopathy
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2019-07-17
Enrollment: 69
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An internally validated CV risk score will be used to determine an individual patient's risk. Low risk patients will be observed and managed according to usual care. Elevated risk patients will be randomized to open label, individually dosed carvedilol for 1 year or usual care.
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: up to 24 months
measure: Treatment adherence as measured by pill count
timeFrame: 12 months
measure: Adverse Events
timeFrame: Up to 24 months
Secondary outcomes:
measure: Diastolic function (E/e') by echocardiogram
timeFrame: up to 24 months
measure: Ventricular-arterial coupling measured by echocardiogram
timeFrame: up to 24 months
measure: Cardiac Strain measurements by echocardiogram
timeFrame: up to 24 months
measure: Frequency of individuals with clinical heart failure
timeFrame: up to 24 months
measure: High-sensitivity Troponin (hsTnT) level
timeFrame: up to 24 months
measure: N-terminal pro B-type natriuetic peptide (NTproBNP) level
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Perelman School of Medicine at the University of Pennsylvania
name: Bonnie Ky, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
References: