Aggressive Lipid Lowering Therapy in ICI-Treated Melanoma

NCT07704918 | Not Yet Recruiting DMC

• 1 other identifier: 25-1921.cc
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Melanoma

Keywords

atherosclerosis; coronary artery disease; coronary atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Mean change in LDL-C from baseline to 12 months

  Each participant will have LDL-C measured prior to randomization and at the 12-month timepoint. The mean change in LDL-C (mg/dL) from baseline to 12 months will be calculated for each participant. The mean change will be compared between the aggressive lipid-lowering therapy arm and the usual care arm.

  Baseline to 12 months

Secondary Outcomes (4)

• Change in Total Plaque Volume from Baseline to 12 months

  12 months

• Major adverse cardiovascular events at 12 months

  12 months

• Change in Calcified Plaque Volume from Baseline to 12 Months

  12 months

• Change in Size of the Largest Plaque from Baseline to 12 Months

  12 months

Study Arms (2)

Active Comparator: Usual Care

NO INTERVENTION

Active Comparator: Usual Care: 12- and 24-month follow-up CCTA with plaque staging, lipid panel

Aggressive Lipid Lowering Therapy

EXPERIMENTAL

Participants in the 'aggressive lipid lowering therapy' arm will receive guideline-directed lipid lowering therapy (statins and/or PCSK9 inhibitors) managed by a cardiologist. Dosing adjustments will be guided by individual patient response and standard-of-care practices, with the goal of achieving LDL-C ≤55 mg/dL.

Drug: Statins (atorvastatin, rosuvastatin, simvastatin, or pravastatin), +/- ezetimibe, +/- PCSK9 inhibitor (alirocumab, evolocumab, inclisiran)

Interventions

Statins (atorvastatin, rosuvastatin, simvastatin, or pravastatin), +/- ezetimibe, +/- PCSK9 inhibitor (alirocumab, evolocumab, inclisiran) DRUG

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.

Aggressive Lipid Lowering Therapy

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Melanoma; Atherosclerosis; Coronary Artery Disease

Interventions

Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium; Simvastatin; Pravastatin; Ezetimibe; alirocumab; evolocumab; ALN-PCS

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Azetidines; Azetines

Study Officials

• Caitlin Bell, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zackry Morgan

CONTACT

720-848-5494; zackry.morgan@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2026
• First Posted: July 15, 2026
• Study Start (Estimated): December 31, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 15, 2026

Record last verified: 2026-07

Locations

US (1)