Cardiotoxicity in Breast Cancer Patients Treated With Proton or Photon Radiotherapy: A RadComp Companion Study

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Cardiotoxicity
• Intervention / Treatment: Radiation: Proton vs Photon Radiation

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 Type: Observational
• Enrollment (Estimated): 175

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama
  • Illinois
    • Warrenville, Illinois, United States, 60555
      • Northwestern Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center at University of Pennsylvania
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients eligible for and enrolling on the RadComp trial at participating RadComp sites will be approached for the companion cohort.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ancillary Cohort; 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.	Radiation: Proton vs Photon Radiation; Assignment to proton vs photon by randomization on RadComp parent study.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
3D LVEF	Change in 3d echocardiography derived LVEF from baseline	14 months
3D LV systolic strain	Change in 3D echocardiography derived longitudinal and circumferential strain from baseline	14 months
LV Twist and Torsion	Change in 3D echocardiography derived measures of LV twist and torsion from baseline	14 months
Patient Reported Outcomes (PRO) Common Terms and Criteria for Adverse Events (CTCAE)	Incidence and severity of PRO CTCAEs	14 months
Incidence of major cardiovascular events (MCE)	Collected, defined, and adjudicated by the RadComp study team	10 years

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Bonnie Ky, MD, MSCE, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: April 6, 2020
• First Submitted That Met QC Criteria: April 23, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Cardio-Oncology; Radiation Therapy Cardiotoxicity
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Wounds and Injuries; Breast Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Breast Neoplasms; Cardiotoxicity
• Other Study ID Numbers: UPCC 17119

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Participants may opt in to allowing data and/or banked samples to be used for future research and shared with other researchers. A detailed plan for sharing IPD will be finalized at a later date, and may depend in part on how many participants elect this option. Additional supporting information may be shared, including the study protocol and informed consent form.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No