Pharmacologic Therapies to Mitigate Radiation- Associated Heart Disease

NCT07685938 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: LCCC2239-DCT
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chest Wall Tumor; Mediastinal Cancers; Lung Cancer; Spinal Tumor; Thoracic Cancer; Breast Cancer; Spine Metastases; Thoracic Neoplasms; Esophageal Cancer

Keywords

radiation therapy; morbidity; mortality; radiation induced heart disease; major adverse cardiac events; placebo-controlled; angiotensin-converting enzyme (ACE) inhibitors; statins

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Percent Change in Radiation-Induced Myocardial Perfusion Reduction by Cardiac Dose: Placebo vs Statin and ACE Inhibitor Therapy

  Pre radiation therapy and 6-month post radiation therapy

• Change in for cardiac biomarker panel

  Pre radiation therapy and 3 months and 6-month post radiation therapy

• Correlation between cardiac stress and perfusion biomarkers and radiation dose

  Pre radiation therapy and 3 months and 6-month post radiation therapy

• Rates of major adverse cardiac events

  At follow-up of 1, 2, and 3 years.

Study Arms (2)

statins and angiotensin-converting enzyme (ACE) inhibitors

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Atorvastatin and Lisinopril DRUG

Patients will receive statins and angiotensin-converting enzyme (ACE) inhibitors.

statins and angiotensin-converting enzyme (ACE) inhibitors

Placebo DRUG

Patients will receive placebo.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead

Study Sites (1)

Lineberger Comprehensive Cancer Center at University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Breast Neoplasms; Lung Neoplasms; Esophageal Neoplasms; Mediastinal Neoplasms; Spinal Cord Neoplasms; Thoracic Neoplasms; Cardiovascular Diseases

Interventions

Atorvastatin; Lisinopril

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Mediastinal Diseases; Thoracic Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Shivani Sud, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Claire Kowalczyk

CONTACT

984-974-0000; claire_kowalczyk@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2026
• First Posted: July 6, 2026
• Study Start: August 12, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: September 17, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)