search
Back to results

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

Primary Purpose

Cardiotoxicity, Risk Factor, Cardiovascular, Toxicity Due to Chemotherapy

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Carvedilol
Sponsored by
Abramson Cancer Center at Penn Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cardiotoxicity focused on measuring Risk-Guided Intervention, Carvedilol, Cardiotoxicity of Chemotherapy, Cardio-Oncology, Cardiomyopathy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Abramson Cancer Center of the University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Carvedilol

Usual Care

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Left Ventricular Ejection Fraction (LVEF)
LVEF derived from quantitative analyses of echocardiography-derived measurements of left ventricular volumes in diastole and systole.
Treatment adherence as measured by pill count
Rate of compliance with prescribed dose of carvedilol by pill count
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.

Secondary Outcome Measures

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.
Ventricular-arterial coupling measured by echocardiogram
Defined by echocardiography-derived measures of end systolic elastance divided by effective arterial elastance
Cardiac Strain measurements by echocardiogram
Echocardiography-derived measures of longitudinal, circumferential, and radial strain.
Frequency of individuals with clinical heart failure
Frequency of clinical heart failure diagnosis
High-sensitivity Troponin (hsTnT) level
Change in the cardiac biomarker of injury hsTnT over time, defined as a continuous variable
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

Full Information

First Posted
March 22, 2019
Last Updated
October 18, 2023
Sponsor
Abramson Cancer Center at Penn Medicine
search

1. Study Identification

Unique Protocol Identification Number
NCT04023110
Brief Title
Risk-Guided Cardioprotection With Carvedilol in Breast Cancer Patients Treated With Doxorubicin and/or Trastuzumab
Acronym
CCTGuide Pilot
Official Title
A Pilot Study of Risk-Guided Cardioprotection With Carvedilol in Breast Cancer Patients Treated With Doxorubicin and/or Trastuzumab
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 9, 2019 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Abramson Cancer Center at Penn Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiotoxicity, Risk Factor, Cardiovascular, Toxicity Due to Chemotherapy, Breast Cancer, Cardiomyopathies, Heart Failure
Keywords
Risk-Guided Intervention, Carvedilol, Cardiotoxicity of Chemotherapy, Cardio-Oncology, Cardiomyopathy

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
69 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Carvedilol
Arm Type
Experimental
Arm Description
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.
Arm Title
Usual Care
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Carvedilol
Other Intervention Name(s)
Coreg
Intervention Description
Individually dosed carvedilol
Primary Outcome Measure Information:
Title
Left Ventricular Ejection Fraction (LVEF)
Description
LVEF derived from quantitative analyses of echocardiography-derived measurements of left ventricular volumes in diastole and systole.
Time Frame
up to 24 months
Title
Treatment adherence as measured by pill count
Description
Rate of compliance with prescribed dose of carvedilol by pill count
Time Frame
12 months
Title
Adverse Events
Description
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.
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Diastolic function (E/e') by echocardiogram
Description
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.
Time Frame
up to 24 months
Title
Ventricular-arterial coupling measured by echocardiogram
Description
Defined by echocardiography-derived measures of end systolic elastance divided by effective arterial elastance
Time Frame
up to 24 months
Title
Cardiac Strain measurements by echocardiogram
Description
Echocardiography-derived measures of longitudinal, circumferential, and radial strain.
Time Frame
up to 24 months
Title
Frequency of individuals with clinical heart failure
Description
Frequency of clinical heart failure diagnosis
Time Frame
up to 24 months
Title
High-sensitivity Troponin (hsTnT) level
Description
Change in the cardiac biomarker of injury hsTnT over time, defined as a continuous variable
Time Frame
up to 24 months
Title
N-terminal pro B-type natriuetic peptide (NTproBNP) level
Description
Change in the cardiac biomarker of neurohormonal stress NT-proBNP over time, defined as a continuous variable
Time Frame
up to 24 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bonnie Ky, MD, MSCE
Organizational Affiliation
Perelman School of Medicine at the University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Abramson Cancer Center of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Investigators do not plan to make the IPD, analytic methods, or study materials available to other researchers for purposes of reproducing our results or replicating the procedure given the pilot Phase 1 nature of this study.

Learn more about this trial

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

We'll reach out to this number within 24 hrs