Cardiotoxicity of Cancer Therapy (CCT)

Breast Cancer Clinical Trial

Official title:

Cardiotoxicity of Cancer Therapy: Mechanisms and Predictors

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT01173341
• Other study ID #: UPCC 09110
• Status: Enrolling by invitation
• Start date: July 2010
• Est. completion date: April 2037

Study information

• Verified date: April 2024
• Source: Abramson Cancer Center at Penn Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 700
• Est. completion date: April 2037
• Est. primary completion date: April 2037
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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:

• Pre-existing cardiomyopathy with a left ventricular ejection fraction of less than 50%.

• Other contraindications to trastuzumab or anthracycline chemotherapy.

Related Conditions & MeSH terms

• Breast Cancer
• Cardiotoxicity

Intervention

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.
• 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.

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	Cardiac dysfunction or signs or symptoms of heart failure	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	Change in quantitated Left Ventricular Ejection Fraction (LVEF)	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