Pharmacologic Therapies to Mitigate Radiation- Associated Heart Disease
Purpose
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
- Breast Cancer
- Lung Cancer
- Esophageal Cancer
- Mediastinal Cancers
- Spine Metastases
- Spinal Tumor
- Thoracic Cancer
- Thoracic Neoplasms
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts 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
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Supportive Care
- Masking
- Single (Participant)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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. |
|
|
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. |
|
Recruiting Locations
Chapel Hill, North Carolina 27599
More Details
- Status
- Recruiting
- Sponsor
- UNC Lineberger Comprehensive Cancer Center