Cardiotoxicity of Cancer Therapy (CCT)

• Conditions: Breast Cancer
• Interventions: Diagnostic Test: Echocardiography; Other: Blood Collection; Other: Symptoms Questionnaire

• Registration Number: NCT01173341
• Lead Sponsor: Abramson Cancer Center at Penn Medicine

Brief Summary

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.

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 Timeline

• Study Start: 2010-07
• Study First Submitted: 2010-07-29
• Study First Submitted QC: 2010-07-29
• Study First Posted: 2010-08-02
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-31
• Last Update Posted: 2025-02-04
• Primary Completion: 2037-04
• Study Completion: 2037-04

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: Female
• Target Recruitment: 700

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Subgroup 2	Symptoms Questionnaire	Subgroup2 represents will undergo trastuzumab therapy only
Subgroup 1	Blood Collection	Subgroup 1 are anthracycline only treated patients.
Subgroup 2	Echocardiography	Subgroup2 represents will undergo trastuzumab therapy only
Subgroup 2	Blood Collection	Subgroup2 represents will undergo trastuzumab therapy only
Subgroup 3	Echocardiography	Subgroup 3 are patients that will undergo trastuzumab therapy with anthracyclines.
Subgroup 3	Blood Collection	Subgroup 3 are patients that will undergo trastuzumab therapy with anthracyclines.
Subgroup 1	Echocardiography	Subgroup 1 are anthracycline only treated patients.
Subgroup 1	Symptoms Questionnaire	Subgroup 1 are anthracycline only treated patients.
Subgroup 3	Symptoms Questionnaire	Subgroup 3 are patients that will undergo trastuzumab therapy with anthracyclines.

Primary Outcome Measures

Name	Time	Method
Cardiac dysfunction or signs or symptoms of heart failure	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

Secondary Outcome Measures

Name	Time	Method
Change in quantitated Left Ventricular Ejection Fraction (LVEF)	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)

Trial Locations

Locations (1)

Abramson Cancer Center of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States