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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atorvastatin and Lisinopril | Drug | Patients will receive statins and angiotensin-converting enzyme (ACE) inhibitors. |
|
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Claire Kowalczyk | Contact | 984-974-0000 | claire_kowalczyk@med.unc.edu |
| Name | Affiliation | Role |
|---|---|---|
| Shivani Sud, MD | UNC Lineberger Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lineberger Comprehensive Cancer Center at University of North Carolina, Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
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| Label | URL |
|---|---|
| University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials | View source |
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| Placebo | Drug | Patients will receive placebo. |
|
| 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. |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D008175 | Lung Neoplasms |
| D004938 | Esophageal Neoplasms |
| D008479 | Mediastinal Neoplasms |
| D013120 | Spinal Cord Neoplasms |
| D013899 | Thoracic Neoplasms |
| D002318 | Cardiovascular Diseases |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012142 | Respiratory Tract Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D008477 | Mediastinal Diseases |
| D013896 | Thoracic Diseases |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| D017706 | Lisinopril |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006538 | Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D004151 | Dipeptides |
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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