ATORVASTATIN for Melanoma | Atherosclerosis

Inclusion criteria

• {"criterion_text":"- Patients with melanoma who are scheduled to receive ICI therapy (nivolumab, pembrolizumab, ipilimumab or combination therapy) according to standard-of-care.\n- Age ≥ 18 years\n- Able to understand the written information and able to give informed consent\n- Presence of thoracic aortic atherosclerosis at baseline, defined as: presence of vessel wall calcifications in the thoracic aorta, and/or vessel wall irregularity of the thoracic aorta, and/or presence of an apparent thickening of the vessel wall with a hypodense aspect in the thoracic aorta"}

Exclusion criteria

• {"criterion_text":"- Baseline statins use or previously reported statin intolerance\n- Pregnancy or lactation\n- Current or recent (≤1 year) history of alcohol (≥3 consumptions/day) or drug abuse\n- Contra-indication for statin therapy, including: active liver disease, including ALT/AST levels ≥ 3x ULN, and/or (History of) myopathy, and/or congenital muscular disorder, and/or history of (drug-induced) rhabdomyolysis, and/or history of drug-induced myopathy with elevated creatine kinase (CK)\n- Use of essential medication with (potential) interactions with atorvastatin, including: Strong CYP3A4 inhibitors (such as clarithromycin, ciclosporin, itraconazole, ketoconazole, voriconazole, posaconazole, HCV agents, HIV protease inhibitors), and/or BCRP inhibitors (such as elbasvir and grazoprevir), and/or Fibrates (including gemfibrozil)\n- Indication for statin treatment according to the 2024 Dutch multi-disciplinary CVRM guidelines\n- Significant obstructive coronary artery disease (>50% LM stenosis or >70% of proximal LAD, Cx or RCA segment, or multivessel significant more distal disease)"}

Primary endpoints

• {"endpoint_text":"- Annualized percentage change in non-calcified atherosclerotic plaque volume in the descending thoracic aorta in the intervention versus the control group.","definition_or_measurement_approach":"Measured as the annualized percentage change in non-calcified atherosclerotic plaque volume in the descending thoracic aorta; comparison between intervention and control groups."}

Secondary endpoints

• {"endpoint_text":"- Annualized percentage change in total and calcified atherosclerotic plaque volume in the thoracic aorta in the intervention versus the control group","definition_or_measurement_approach":"Annualized percentage change in total and calcified plaque volume in the thoracic aorta; comparison between intervention and control groups."}
• {"endpoint_text":"- Annualized percentage change in total, non-calcified and calcified coronary artery atherosclerotic plaque volume in the intervention versus the control group.","definition_or_measurement_approach":"Annualized percentage change in total, non-calcified and calcified coronary artery plaque volume; comparison between intervention and control groups."}
• {"endpoint_text":"- Annualized change in coronary calcification score (Agatston score) and MESA score in the intervention versus the control group.","definition_or_measurement_approach":"Annualized change in coronary Agatston score and MESA score; comparison between intervention and control groups."}
• {"endpoint_text":"- Annualized change in epicardial fat volume in the intervention versus the control group p","definition_or_measurement_approach":"Annualized change in epicardial fat volume; comparison between intervention and control groups."}
• {"endpoint_text":"- Difference in reactive hyperaemia index as a marker of endothelial dysfunction using peripheral arterial tonometry (EndoPAT) between intervention and control group.","definition_or_measurement_approach":"Reactive hyperaemia index measured by peripheral arterial tonometry (EndoPAT); difference between intervention and control groups."}
• {"endpoint_text":"- Difference in quality of life between intervention and control group at baseline, 3 months, 6 months and 1 year after the start of ICI therapy","definition_or_measurement_approach":"Quality of life assessed at baseline, 3 months, 6 months and 1 year after ICI start; comparison between intervention and control groups."}
• {"endpoint_text":"- Differences in the number of adverse events between intervention and control group during the first year after start of ICI therapy, graded according to CTCAE criteria, version 5.0.","definition_or_measurement_approach":"Adverse events during first year after ICI start graded according to CTCAE v5.0; comparison of event counts between groups."}

Netherlands

Earliest CTIS Part Ii Submission Date

22-04-2025

Latest Decision Or Authorization Date

12-05-2025

Processing Time Days

20

Number Of Sites

2

Number Of Participants

172

Primary sponsor

Full Name

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands