Pharmacologic Therapies to Mitigate Radiation- Associated Heart Disease

Radiation therapy is an essential treatment for tumors in the chest area, including breast, lung, esophageal, mediastinal cancers, and spine metastases. Although technical advances have reduced treatment-related illness and death, radiation exposure to the heart can still cause substantial rates of radiation-induced heart disease (RIHD) among survivors.

For example, about 21% of non-small cell lung cancer patients receiving a mean heart dose of 20 Gy or higher experience major adverse cardiac events (MACE) within 2 years. In breast cancer patients, the risk of MACE increases by about 7% for each additional Gy of mean heart dose.

There is currently no established medication strategy to prevent or reduce RIHD.

Preclinical and clinical studies show that statins and angiotensin-converting enzyme (ACE) inhibitors may help reduce radiation-induced heart disease (RIHD). Statins and ACE inhibitors are generally well tolerated, available as generic drugs, and commonly used to help prevent cardiovascular disease. They may protect the heart by reducing damage to blood vessel lining (endothelial damage), microvascular dysfunction, atherosclerosis, reduced blood flow (ischemia), and fibrosis (scarring).

This study is a prospective, randomized, placebo-controlled phase II hybrid decentralized trial. Patients receiving standard radiation therapy and expected to receive an equivalent dose of at least 25 Gy (EQD2) to at least 10% of the heart will be randomly assigned to receive either:

• placebo, or
• Atorvastatin 20 mg plus Lisinopril 5 mg daily. The medications will be taken during radiation therapy and continued for 6 months after treatment.

The study aims to determine whether the intervention can reduce radiation-related decreases in blood flow to the heart, measured using myocardial perfusion imaging, such as positron emission tomography (PET), which is commonly used to evaluate the risk of coronary heart disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Thoracic Neoplasms; Esophageal Cancer; Lung Cancer; Thoracic Cancer; Spinal Tumor; Spine Metastases; Chest Wall Tumor; Mediastinal Cancers
• Intervention / Treatment: Drug: Placebo; Drug: Atorvastatin and Lisinopril

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Claire Kowalczyk; Phone Number: 984-974-0000; Email: claire_kowalczyk@med.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Lineberger Comprehensive Cancer Center at University of North Carolina, Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent obtained to participate in the study and HIPAA
• authorization for release of personal health information.
• Subjects is willing and able to comply with study procedures based on the
• judgement of the investigator.
• Consent for serial blood draws and consent for use of biological specimens.
• Age ≥ 18 years at the time of consent

Exclusion Criteria:

• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Pre-existing use of a statin or ACE-inhibitor
• Pre-existing hypotension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: statins and angiotensin-converting enzyme (ACE) inhibitors; Patients expected to receive ≥25 Gy equivalent dose in 2 Gy fractions (EQD2) to at least 10% of the heart will be treated with statins and angiotensin-converting enzyme (ACE) inhibitors.	Drug: Atorvastatin and Lisinopril; Patients will receive statins and angiotensin-converting enzyme (ACE) inhibitors.
Placebo Comparator: Placebo; Patients expected to receive ≥25 Gy equivalent dose in 2 Gy fractions (EQD2) to at least 10% of the heart will take inhibitors.	Drug: Placebo; Patients will receive placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent difference in the radiation (RT)-induced reduction of myocardial perfusion	Percent difference in the radiation (RT)-induced reduction of myocardial perfusion in cardiac regions receiving ≥25Gy equivalent dose in 2Gy fractions (EQD2) based on comparison of before and after RT among participants receiving placebo and statins and angiotensin-converting enzyme (ACE) inhibitors intervention.	Pre radiation therapy and 6-month post radiation therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Radiation-Induced Myocardial Perfusion Reduction by Cardiac Dose: Placebo vs Statin and ACE Inhibitor Therapy	Percent difference in radiation therapy (RT)-induced reduction of myocardial perfusion in cardiac regions receiving different radiation doses (10-20 Gy and 20-25 Gy equivalent dose in 2 Gy fractions, EQD2), based on comparison of pre-RT and 6-month post-RT myocardial perfusion imaging scans between participants receiving placebo versus statins and angiotensin-converting enzyme (ACE) inhibitors intervention.	Pre radiation therapy and 6-month post radiation therapy
Change in for cardiac biomarker panel	Change in for cardiac biomarker panel including high- sensitivity troponin, Creatine Kinase myocardial band (CK-MB) or N-terminal pro-B-type Natriuretic Peptide( NT-proBNP).	Pre radiation therapy and 3 months and 6-month post radiation therapy
Correlation between cardiac stress and perfusion biomarkers and radiation dose	Correlations between absolute values and changes in cardiac stress/perfusion biomarkers and radiation dose at the individual pixel level will be compared between the placebo and intervention groups. Cardiac perfusion imaging provides quantitative assessment of regional myocardial perfusion, and the absolute difference in RT-induced perfusion reduction between study arms will be evaluated using pre- and post-RT measurements. Changes in cardiac biomarkers, including high- sensitivity troponin, Creatine Kinase myocardial band (CK-MB) or N-terminal pro-B-type Natriuretic Peptide( NT-proBNP). will also be assessed.	Pre radiation therapy and 3 months and 6-month post radiation therapy
Rates of major adverse cardiac events	Rates of major adverse cardiac events (unstable angina, heart failure hospitalization or urgent visit, myocardial infarction, coronary revascularization, and cardiac death) will be compared between trial groups at long-term	At follow-up of 1, 2, and 3 years.

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Investigators: Principal Investigator: Shivani Sud, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: June 29, 2026
• First Submitted That Met QC Criteria: June 29, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: mortality; radiation therapy; placebo-controlled; morbidity; statins; major adverse cardiac events; radiation induced heart disease; angiotensin-converting enzyme (ACE) inhibitors
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Lung Diseases; Head and Neck Neoplasms; Respiratory Tract Neoplasms; Esophageal Diseases; Skin Diseases; Breast Diseases; Nervous System Neoplasms; Central Nervous System Neoplasms; Spinal Cord Diseases; Mediastinal Diseases; Thoracic Diseases; Skin and Connective Tissue Diseases; Lung Neoplasms; Cardiovascular Diseases; Esophageal Neoplasms; Breast Neoplasms; Thoracic Neoplasms; Spinal Cord Neoplasms; Mediastinal Neoplasms; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fatty Acids; Lipids; Azoles; Pyrroles; Heptanoic Acids; Dipeptides; Atorvastatin; Lisinopril
• Other Study ID Numbers: LCCC2239-DCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No