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

Breast Cancer Clinical Trial

— CCTGuide Pilot  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04023110
• Other study ID #: UPCC12118
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 9, 2019
• Est. completion date: December 31, 2024

Study information

• Verified date: October 2023
• Source: Abramson Cancer Center at Penn Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 69
• Est. completion date: December 31, 2024
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Carvedilol
Individually dosed carvedilol

Locations

Country	Name	City	State
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Abramson Cancer Center at Penn Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Left Ventricular Ejection Fraction (LVEF)	LVEF derived from quantitative analyses of echocardiography-derived measurements of left ventricular volumes in diastole and systole.	up to 24 months
Primary	Treatment adherence as measured by pill count	Rate of compliance with prescribed dose of carvedilol by pill count	12 months
Primary	Adverse Events	Adverse Events will be assessed using the CTCAE v5.0. The number of Grade 2-5 toxicities observed will be tabulated by risk group and by treatment arm. Differences will be evaluated using Fisher exact tests.	Up to 24 months
Secondary	Diastolic function (E/e') by echocardiogram	The mitral valve inflow velocity divided by the average early diastolic tissue velocities of the mitral valve annulus (septal, lateral) measured by tissue Doppler echocardiography.	up to 24 months
Secondary	Ventricular-arterial coupling measured by echocardiogram	Defined by echocardiography-derived measures of end systolic elastance divided by effective arterial elastance	up to 24 months
Secondary	Cardiac Strain measurements by echocardiogram	Echocardiography-derived measures of longitudinal, circumferential, and radial strain.	up to 24 months
Secondary	Frequency of individuals with clinical heart failure	Frequency of clinical heart failure diagnosis	up to 24 months
Secondary	High-sensitivity Troponin (hsTnT) level	Change in the cardiac biomarker of injury hsTnT over time, defined as a continuous variable	up to 24 months
Secondary	N-terminal pro B-type natriuetic peptide (NTproBNP) level	Change in the cardiac biomarker of neurohormonal stress NT-proBNP over time, defined as a continuous variable	up to 24 months