Aggressive Lipid Lowering Therapy in ICI-Treated Melanoma

Official title

Lipid Lowering Therapy for Atherosclerotic Disease in Melanoma Patients Receiving Immune Checkpoint Inhibitors

Overview

Immune checkpoint inhibitors (ICIs) are a class of medications that are now standard in the treatment of melanoma. These are standard therapy for melanoma, but long-term side effects on disease in the heart arteries is poorly understood. In this study, melanoma patients receiving ICIs for the first time will undergo a coronary computed tomography angiography (CCTA) scan. CCTA results will be analyzed by the FDA-approved Cleerly TM image analysis pipeline. Patients with disease in their heart arteries will be randomized to usual care or aggressive lipid lowering therapy. Those in the aggressive lipid lowering therapy arm will be seen by a cardiologist and placed on standard lipid lowering medications with a goal of achieving an LDL-C ≤ 55mg/dL. Follow-up CCTA scans will occur at 12-month and 24-month timepoints. The primary outcome of interest will be differences in LDL-C levels between the two arms at the 12-month timepoint. The secondary outcome of interest will be the differences in total plaque volume between the two arms at the 12-month timepoint.

Interventions

• Drug Statins (atorvastatin, rosuvastatin, simvastatin, or pravastatin), +/- ezetimibe, +/- PCSK9 inhibitor (alirocumab, evolocumab, inclisiran)
  Participants randomized to the aggressive lipid lowering therapy arm will receive Guideline-directed lipid-lowering therapy (statins and/or ezetimibe and/or PCSK9 inhibitors) managed by a cardiologist with dose adjustments to achieve LDL-C ≤55 mg/dL.

Primary outcome measures

• Mean change in LDL-C from baseline to 12 months [Time frame: Baseline to 12 months]

Secondary outcome measures (4)

• Change in Total Plaque Volume from Baseline to 12 months [Time frame: 12 months]
• Major adverse cardiovascular events at 12 months [Time frame: 12 months]
• Change in Calcified Plaque Volume from Baseline to 12 Months [Time frame: 12 months]
• Change in Size of the Largest Plaque from Baseline to 12 Months [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Provision to sign and date the consent form.
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Be a male aged ≥55 years or a female aged ≥65 years.
• For those able to bear children, documentation of menopausal status via approximate last menstrual period or hysterectomy due to contraindication of pregnancy for the CCTA procedure.
• Have a melanoma diagnosis without prior ICI use and planning to start on ICI therapy (PD-1, PD-L1, CTLA-4, LAG3) as standard of care for their cancer.
• Plaque stage ≥ 1 on screening CCTA.

Exclusion criteria

• Any prior major cardiovascular event, defined as myocardial infarction, stroke, coronary revascularization, or other major cardiovascular event determined to be significant by the principal investigator.
• Meeting any of the standard CCTA contraindications listed below:
• Allergy to iodinated contrast or history of contrast-induced nephropathy
• Renal insufficiency (eGFR < 45 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) or Modification of Diet in Renal Disease (MDRD) equation). A current eGFR value (collected/calculated within 3 months from screening visit) is required at baseline.
• Active arrhythmia (atrial fibrillation, atrial flutter, frequent premature atrial, or ventricular contractions) with poorly controlled rate (i.e., > 80 beats per minute). EKG must be performed within 1 year of screening visit.
• Hemodynamic instability
• Weight > 400 lbs. (181 kg) or above manufacturer-recommended limit for scanner and table, whichever is lower
• Thyroid cancer in the previous five (5) years or planned radioactive iodine treatment
• Pregnancy
• Inability to hold breath for > 10 seconds
• Contraindication to dosing with beta blocker as needed or nitroglycerin prior to CCTA procedure
• Inability to cooperate with scan acquisition and/or breath-hold instructions
• Any other factor that, in the opinion of the investigator, would increase participant risk or increase the chance of an uninterpretable CCTA
• If a patient's fast LDL-C is > 190 mg/dL, this is consistent with underlying familial hypercholesterolemia, and they will not be eligible for the study.
• If a patient's CCTA demonstrates previously undiagnosed obstructive coronary disease, they will not be eligible for the study. Obstructive disease will be defined as >50% obstruction in the left main coronary artery, or >70% obstruction elsewhere in the coronary tree.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Colorado Hospital — Aurora

Identifiers

NCT: NCT07704918 · 25-1921.cc

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗