Breast Cancer, Chest Wall Tumor, Esophageal Cancer, Lung Cancer, Mediastinal Cancers, Spinal Tumor, Spine Metastases, Thoracic Cancer, Thoracic Neoplasms
Conditions
Keywords
radiation therapy, morbidity, mortality, radiation induced heart disease, major adverse cardiac events, placebo-controlled, angiotensin-converting enzyme (ACE) inhibitors, statins
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.
Interventions
DRUGAtorvastatin and Lisinopril
Patients will receive statins and angiotensin-converting enzyme (ACE) inhibitors.
DRUGPlacebo
Patients will receive placebo.
Sponsors
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent difference in the radiation (RT)-induced reduction of myocardial perfusion | Pre radiation therapy and 6-month post radiation therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Change in for cardiac biomarker panel | Pre radiation therapy and 3 months and 6-month post radiation therapy | 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). |
| Correlation between cardiac stress and perfusion biomarkers and radiation dose | Pre radiation therapy and 3 months and 6-month post radiation therapy | 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. |
| Rates of major adverse cardiac events | At follow-up of 1, 2, and 3 years. | 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 |
Countries
United States
Contacts
CONTACTClaire Kowalczyk
PRINCIPAL_INVESTIGATORShivani Sud, MD
UNC Lineberger Comprehensive Cancer Center
Outcome results
None listed