Cardiotoxicity of Cancer Therapy (CCT)

February 5, 2026 updated by: Abramson Cancer Center at Penn Medicine

Cardiotoxicity of Cancer Therapy: Mechanisms and Predictors

The objective of this study is to define the clinical significance of mechanistic biomarkers (including Neuregulin-1Beta) and novel echocardiographic measures of cardiac function in predicting the incident risk of cancer therapy cardiotoxicity.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

The overall study objectives are:

  1. To determine the longitudinal relationships between circulating markers, such as Neuregulin (NRG)-1Beta levels and incident risk of adverse cardiovascular outcomes in patients exposed to anthracycline, trastuzumab, or a combination of the two agents. We hypothesize that a sustained increase in NRG-1Beta, indicative of enhanced cardiac stress with exposure to chemotherapeutic agents, is predictive of an increased risk of cardiac dysfunction and heart failure.
  2. To study the single nucleotide polymorphism (SNP)/haplotype variation in pathways of interest, such as the Neuregulin/Epidermal Growth Factor (ErbB) signaling pathway, on incident risk of adverse cardiovascular outcomes. We hypothesize that there will be SNP/haplotypes variations that are associated with incident cardiovascular outcomes.
  3. To determine the longitudinal relationships between novel echocardiographic measures, such as strain and strain rate and incident cardiac dysfunction in patients exposed to anthracycline, trastuzumab, or a combination of the two agents. We hypothesize that early declines in strain and strain rate are predictive of an increased risk of future cardiac dysfunction and heart failure.
  4. To explore the changes in biomarkers such as NRG-1Beta levels and the relationships with novel echocardiographic measures of cardiac function.
  5. To create a biobank as a future resource for additional questions in novel biomarkers and genetics.
  6. To determine the long-term effects of cancer therapy cardiotoxicity by following patients yearly for 5 years after their exposure to cancer therapy, with the option to extend up to an additional 5 years.

Study Type

Observational

Enrollment (Estimated)

700

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Abramson Cancer Center of The University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Subjects with breast cancer will enter the cohort prior to chemotherapy initiation and be evaluated at baseline and at regular intervals during the first approximately 15 months after chemotherapy is initiated. Patients will have study visits at 2 years, 3 years, 5, years, 7 years, 9 years, 11 years, 13 years, and 15 years following initiation of cancer therapy.

Description

Inclusion Criteria:

  • Age 18 years or older
  • HER-2 positive breast cancer designated to receive trastuzumab chemotherapy with or without prior exposure to anthracycline-based chemotherapy
  • Non-HER-2 positive breast cancer designated to receive treatment with an anthracycline-containing regimen

Exclusion Criteria:

  • Other contraindications to trastuzumab or anthracycline chemotherapy.
  • Vulnerable populations

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Subgroup 2
Subgroup2 represents will undergo trastuzumab therapy only
Diagnostic test: Echocardiography
Prior to chemotherapy, prior to and after anthracyclines, every 6 weeks during trastuzumab, and yearly for up to 10 years.
Other: Blood Collection
Drawn at first chemo treatment and periodically during treatment (exact schedule varies with clinically ordered treatment plan), then annually for up to 10 years. Blood is banked for future biomarker testing.
Other: Symptoms Questionnaire
Survey collected at first chemotherapy, periodically during therapy (exact schedule determined by clinically ordered treatment regimen), and annually for up to 10 years.
Subgroup 1
Subgroup 1 are anthracycline only treated patients.
Diagnostic test: Echocardiography
Prior to chemotherapy, prior to and after anthracyclines, every 6 weeks during trastuzumab, and yearly for up to 10 years.
Other: Blood Collection
Drawn at first chemo treatment and periodically during treatment (exact schedule varies with clinically ordered treatment plan), then annually for up to 10 years. Blood is banked for future biomarker testing.
Other: Symptoms Questionnaire
Survey collected at first chemotherapy, periodically during therapy (exact schedule determined by clinically ordered treatment regimen), and annually for up to 10 years.
Subgroup 3
Subgroup 3 are patients that will undergo trastuzumab therapy with anthracyclines.
Diagnostic test: Echocardiography
Prior to chemotherapy, prior to and after anthracyclines, every 6 weeks during trastuzumab, and yearly for up to 10 years.
Other: Blood Collection
Drawn at first chemo treatment and periodically during treatment (exact schedule varies with clinically ordered treatment plan), then annually for up to 10 years. Blood is banked for future biomarker testing.
Other: Symptoms Questionnaire
Survey collected at first chemotherapy, periodically during therapy (exact schedule determined by clinically ordered treatment regimen), and annually for up to 10 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiac dysfunction or signs or symptoms of heart failure
Time Frame: 15 years
Cardiac dysfunction. as defined according to the Cardiac Review and Evaluation Committee (CREC) criteria as a decline in LVEF of 10% to less than 55% without signs or symptoms
15 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in quantitated Left Ventricular Ejection Fraction (LVEF)
Time Frame: 15 years
Change in LVEF over the course of chemotherapy; incident diastolic dysfunction by echocardiography; the combined endpoint of any incident adverse cardiovascular outcome (arrhythmia, heart failure, systolic dysfunction, or diastolic dysfunction by echo)
15 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abramson Cancer Center at Penn Medicine

Investigators

  • Principal Investigator: Bonnie Ky, MD, Abramson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2010

Primary Completion (Estimated)

April 1, 2037

Study Completion (Estimated)

April 1, 2037

Study Registration Dates

First Submitted

July 29, 2010

First Submitted That Met QC Criteria

July 29, 2010

First Posted (Estimated)

August 2, 2010

Study Record Updates

Last Update Posted (Actual)

February 9, 2026

Last Update Submitted That Met QC Criteria

February 5, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UPCC 09110

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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