Statins and prOgression of Coronary atheRosclerosis in melanomA Patients Treated With chEckpoint inhibitorS

Study Overview
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Brief Summary
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This study will incorporate a prospective randomised open blinded end-point trial in participants with stage 2, 3 or 4 melanoma treated with ICI to evaluate the impact of statin therapy on changes in coronary plaque burden and composition.

Official Title
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Statins and prOgression of Coronary atheRosclerosis in melanomA Patients Treated With chEckpoint inhibitorS

Conditions
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Melanoma, Atherosclerosis

Intervention / Treatment
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* Drug: Atorvastatin Calcium 40Mg Tab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients aged > or equal to 40 years diagnosis of stage 2, 3 or 4 melanoma treated with an ICI not currently treated with a statin ,and having acceptable imaging quality deemed by the core laboratory Exclusion Criteria: inability to provide informed consent unwilling to be followed for serial evaluation contra-indication or intolerance to statins clinically manifest CV disease prognostic factors associated with an expected survival less than 18 months (eg. un-resectable brain metastases) severe liver disease or advanced renal disease (³stage 3b CKD or eGFR <45 ml/min) any other factor that will preclude patients from participating in all study related activities

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Statin treatment<br>Atorvastatin 40mg, daily, orally for 18 months | Drug: Atorvastatin Calcium 40Mg Tab<br>* One tablet daily<br>|
| No Intervention: No statin treatment<br>No comparator treatment/placebo allocated | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in non-calcified plaque volume according to treatment with statins | Difference in non-calcified plaque volume as measured on serial CTCA between patients treated with and without statin therapy | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total plaque volume in patients treated with ICI compared to historical cohorts | Difference in total plaque volume as measured on serial CTCA between patients treated with ICI therapy against historical cohorts | 18 months | 
| Change in pericoronary adipose tissue attenuation and volume according to treatment with statins | Difference in pericoronary adipose tissue attenuation and volume as measured on serial CTCA between patients treated with and without statin therapy | 18 months | 
| Cost-effectiveness of the use of CTCA as measured by net costs per life year gained in patients with melanoma treated with ICI therapy | Differences in cost-effectiveness ratios in terms of net costs per life year gained between patients with melanoma treated with ICI therapy who had CTCA performed compared to historical cohorts who did not have CTCA performed | 18 months | 
| Incidence of adverse events with statin therapy | Incidence and number of patients treated with and without statin therapy with reported adverse events and serious adverse events | 18 months | 
| Cost-effectiveness of statin therapy in patients with melanoma treated with ICI therapy as measured by net costs per life year gained | Difference in cost-effectiveness ratios between patients with melanoma on ICI therapy who are treated with and without statin therapy, in terms of net costs per life year gained | 18 months | 
| Effect of statins on depression in patients with melanoma treated with ICI therapy as measured on the Patient Health Questionnaire-9 | Differences in mean changes in scores for the Patient Health Questionnaire-9 for each patient according to statin use, with a minimum score of 0 and a maximum score of 27, and higher scores indicating higher likelihood of depression | 18 months | 
| Effect of statins on anxiety in patients with melanoma treated with ICI therapy as measured on the Generalized Anxiety Disorder-7 questionnaire | Differences in mean changes in scores for the Generalized Anxiety Disorder-7 questionnaire for each patient according to statin use, with a minimum score of 0 and a maximum score of 21, and higher scores indicating higher likelihood of anxiety | 18 months | 
| Effect of statins on quality of life in patients with melanoma treated with ICI therapy as measured on the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire | Differences in mean changes in scores for the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire for each patient according to statin use, with a minimum score of 30 and a maximum score of 126, and higher scores indicating poorer quality of life | 18 months | 
| Effect of statins on quality of life in patients with melanoma treated with ICI therapy as measured on the EuroQoL Group EQ-5D questionnaire | Differences in mean changes in scores for the EuroQoL Group EQ-5D questionnaire for each patient according to statin use, with a minimum score of 1 and a maximum score of 15, and higher scores indicating poorer quality of life | 18 months | 
| Effect of statins on quality of life in patients with melanoma treated with ICI therapy as measured on the FACT-M questionnaire | Differences in mean changes in scores for each section of the FACT-M questionnaire for each patient according to statin use. The score ranges for each individual section are: physical well-being 0-28, social well-being 0-28, emotional well-being 0-24, functional well-being 0-28, additional well-being 0-64, and melanoma-specific questions 0-32. Interpretation of scoring depends on the individual sections in the questionnaire, with higher scores in the physical, emotional, additional and melanoma-specific questions indicating poorer quality of life, whilst lower scores in the social and emotional questions indicate poorer quality of life | 18 months |