Cardiotoxicity in Breast Cancer Patients Treated with Proton or Photon Radiotherapy: a RadComp Companion Study

Active, not recruiting

• Conditions: Breast Cancer; Cardiotoxicity
• Interventions: Radiation: Proton vs Photon Radiation

• Registration Number: NCT04361240
• Lead Sponsor: Abramson Cancer Center at Penn Medicine

Brief Summary

This is a companion study to the "Pragmatic Randomized Trial of Proton vs Photon Therapy for Patients with non-Metastatic Breast Cancer Receiving Comprehensive Nodal Radiation: A Radiotherapy Comparative Effectiveness (RadComp) Consortium Trial" (NCT02603341). The investigators will collect cardiovascular (CV) biomarkers and echocardiograms prior to, during, and for up to 1 year following radiation for a subset of patients enrolled on RadComp and to evaluate the impact of proton vs photon radiation therapy (RT) on CV function and structure.

Detailed Description

The study population of the companion study will consist of newly enrolled RadComp trial participants. Patients on this ancillary will be consented prior to RadComp randomization to decrease the bias secondary to RT type and enhance internal validity. The study will define the early changes in biomarkers, imaging measures, and RT dose volume metrics and long-term (5-10 year) CV clinical outcomes using the RadComp parent study's infrastructure for clinical data collection and long-term follow-up. Blood samples, echocardiograms, and questionnaires are obtained at baseline (between end of chemotherapy and start of RT), immediately after the end of RT, and at 6 months and 12 months after the end of RT. An additional blood sample will be collected at 4 weeks after the start of RT. Clinical, demographic, and patient reported outcomes data are collected as part of the RadComp parent study. In addition to data collected by RadComp, we will collect a limited set of clinical data and two additional quality of life instruments for the companion study.

Study Timeline

• Study First Submitted: 2020-04-06
• Study First Submitted QC: 2020-04-23
• Study First Posted: 2020-04-24
• Study Start: 2020-08-01
• Status Verified: 2024-04
• Last Update Submitted: 2024-10-08
• Last Update Posted: 2024-10-10
• Primary Completion: 2025-04
• Study Completion: 2025-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 175

Inclusion Criteria

• Consented to RadComp
• Willing and able to provide written consent

Exclusion Criteria

• Knowledge of randomization on RadComp prior to enrollment on companion study
• Non-diagnostic echocardiography windows as assessed on local read.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Ancillary Cohort	Proton vs Photon Radiation	No Intervention: Subjects will be followed before, during and for up to 1 year after radiation with echocardiogram, blood draw, and symptoms and activity survey.

Primary Outcome Measures

Name	Time	Method
Left ventricular ejection fraction (LVEF)	14 months	Change in echocardiography derived LVEF from baseline
Circulating Growth Differentiation Factor-15 (GDF-15)	14 months	Change in GDF-15 levels from baseline
Right Ventricular (RV) Fractional Area Change (FAC)	14 months	Change in echocardiography derived RV FAC from baseline
Circulating N-terminal pro B-type natriuretic peptide (NTproBNP)	14 months	Change in NTproBNP levels from baseline
Circulating Placental Growth Factor (PIGF)	14 months	Change in PIGF levels from baseline

Secondary Outcome Measures

Name	Time	Method
Diastolic function (E/e')	14 months	Change in E/e' from baseline as measured by echocardiogram
Echocardiography derived Ventricular Arterial Coupling Measurement	14 months	Change from baseline in ventricular arterial coupling as defined by end systolic elastance divided by effective arterial elastance
LV systolic strain	14 months	Change in 2D echocardiography derived LV global longitudinal strain and circumferential strain from baseline
Circulating Troponin T(TnT)	14 months	Change in high-sensitivity TnT levels from baseline
Circulating high-sensitivity C-Reactive Protein (hsCRP)	14 months	Change in hsCRP levels from baseline

Trial Locations

Locations (6)

Northwestern Medicine; 🇺🇸 Warrenville, Illinois, United States

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

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States

University of Washington; 🇺🇸 Seattle, Washington, United States