Statins to Prevent Immune Checkpoint Inhibitor-induced PRogression of AtherosLerosis

NCT06785974 | Not Yet Recruiting Phase 4

• 1 other identifier: 11670
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this interventional study is to test whether atorvastatin prevents accelerated progression of atherosclerosis in melanoma patients who receive immune checkpoint inhibitor (ICI) therapy. The main questions it aims to answer are:

• difference in percentage growth of total atherosclerotic plaque volume (+ calcified and non-calcified plaque volume) in the descending thoracic segment of the aorta
• difference in percentage growth of total atherosclerotic plaque volume (+ calcified and non-calcified plaque volume) in coronary arteries. Researchers will compare patients that receive ICI-therapy and atorvastatin with patients that receive ICI-therapy + placebo to see if atorvastatin will prevent accelerated ICI induced plaque growth.

Conditions

Atherosclerosis; Melanoma; Immune-related Adverse Event

Keywords

Statin; Immune Checkpoint Inhibitor

Outcome Measures

Primary Outcomes (1)

• Percentual annual growth of atherosclerotic plaques in the descending thoracic aorta

  The percentage difference in atherosclerotic plaque volume in the descending part of the thoracic after 1 year of ICI-therapy will be compared to the atherosclerotic plaque volume at baseline.

  1 year

Secondary Outcomes (7)

• Difference in percentage increase in non-calcified and calcified atherosclerotic plaque volume in the descending thoracic aorta

  1 year

• Difference in percentage increase in total, non-calcified and calcified coronary artery atherosclerotic plaque volume

  1 year

• Difference in increase in coronary calcification score (Agatston score) and Multi-Ethnic Study of Atherosclerosis (MESA) score

  1 year

• Difference in change in epicardial fat volume

  1 year

• Difference in reactive hyperaemia in-dex

  1 year

Other Outcomes (5)

• The effect of atorvastatin on median Progression Free Survival in months

  1 and 3 years

• The effect of statins on the median Overall Survival in months

  1 and 3 years

• The effect of statins on the median Event Free Survival in months

  1 and 3 years

Study Arms (2)

Intervention/ Atorvastatin arm

EXPERIMENTAL

Patient will receive 20mg of atorvastatin daily together with ICI-therapy

Drug: Atorvastatin

Placebo arm

PLACEBO COMPARATOR

Patient will receive placebo daily together with ICI-therapy

Drug: Placebo

Interventions

Atorvastatin DRUG

Daily 20mg atorvastatin.

Also known as: Lipitor, Atorvastatin Mylan

Intervention/ Atorvastatin arm

Placebo DRUG

Daily Placebo in combination with ICI-therapy

Placebo arm

Eligibility Criteria

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

You may qualify if:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Age ≥ 18 years
• Able to understand the written information and able to give informed consent
• Melanoma diagnosis with planned ICI treatment according to standard of care (nivolumab, pembrolizumab, monotherapy or combination therapy with ipilimumab)
• Presence of atherosclerosis in the descending thoracic aorta at baseline.

You may not qualify if:

• Pregnancy or lactation
• Baseline statin use or previously reported statin intolerance
• Current or recent (≤1 year) history of alcohol or drug abuse
• Contra-indication for statin therapy, including:
• Active liver disease, including ALT/AST levels ≥ 3x ULN
• (History of) myopathy Congenital muscular disorder History of (drug-induced) rhabdomyolysis History of drug-induced myopathy with elevated creatine kinase (CK)
• Severe kidney failure (creatinine clearance \< 30 ml/min)
• Use of essential medication with (potential) interactions with atorvastatin, including:
• strong CYP3A4 inhibitors such as clarithromycin, ciclosporin, itraconazol, ketoconazole, voriconazol, posconazol, HCV agents, HIV protease inhibitors
• BCRP inhibitors such as elbasvir and grazoprevir
• Fibrates (including gemfibrozil)
• Life expectancy \< 12 months
• High MESA-score at baseline

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Amphia Hospital: collaborator

Study Sites (1)

Erasmus Universitair Medisch Cetrum Rotterdam

Rotterdam, South Holland, 3015GD, Netherlands

Location

Related Links

• Maarten van der Weijden Foundation

MeSH Terms

Conditions

Atherosclerosis; Melanoma

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; 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

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Jorie Versmissen, MD,PhD

  Department Internal Medicine, Hospital Pharmacy, Erasmus MC Rotterdam

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tom Uyl, MD

CONTACT

010-7033202; t.uyl@erasmusmc.nl

Jorie Versmissen, MD, PhD

CONTACT

010-7033202; j.versmissen@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 16, 2024
• First Posted: January 22, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2030
• Last Updated: January 22, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: 2 years inclusion, 1 year after completion, 1 year analysis approximately 01-08-2028. Data will be available for 15 years after date of obtaining.
• Access Criteria: The data will only become available after the study has been completed for at least 1 year. After completion of the study, the Erasmus MC policy for requesting data will be applied. Furthermore, the General Data Protection Regulation must be complied with at all times.

Locations

NL (1)