Cognitive Function in Melanoma Patients Treated With Adjuvant Immune Checkpoint Inhibitors

Cognitive Function in Patients Treated for Melanoma With Adjuvant Immune Checkpoint Inhibitors: A Controlled Prospective Observational Study

Immune checkpoint inhibitors (ICIs) are a group of novel immunotherapies that boost the body's own defense against the cancer by improving the immune system's ability to recognize and destroy cancer cells. While it is relatively well-documented that conventional cancer treatments (e.g., chemotherapy) are associated with cognitive impairment, virtually nothing is yet known about effects on cognition during and after ICI treatment. Due to significantly improved survival rates after ICI treatments, it becomes important to map possible adverse effects associated with these treatments. The investigators therefore investigate possible changes in cognitive function in a group of cancer patients from prior to ICI treatment to nine months later. A gender- and age- matched healthy control group will serve as a comparison. The study has the potential to broaden our understanding of associations between cognition, the brain, and the immune system and to provide clinically relevant knowledge about possible cognitive impairments associated with immunotherapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Quality of Life; Inflammation; Fatigue; Cognitive Impairment; Sleep; Depression, Anxiety; Cancer-related Cognitive Impairment; Sickness Behavior

Detailed Description

This controlled prospective observational study will include two groups with a total of 84 participants. A total of 42 patients diagnosed with melanoma, referred to treatment with ICI will be enrolled in the study and examined prior to treatment with ICI (baseline), at eight weeks following baseline (T2), at 24 weeks following baseline (T3) and 12 weeks after treatment completed (T4). A total of 42 gender- and age- matched healthy controls will be included and assessed at similar time points. Assessments will include a battery of neuropsychological tests, questionnaires, blood samples, and Magnetic Resonance Imaging (MRI).

The main objectives of the study are to investigate:

1. Changes in cognitive functions over the course of treatment with ICIs.
2. Possible associations between changes in cognitive function and immune markers during and following ICI treatment.
3. Possible associations between changes in cognitive function and changes in brain morphology.
4. Changes over time in other possible adverse effects of ICI treatment, including psychological distress, sleep disturbances, and fatigue.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with melanoma and scheduled for ICI treatment at Aarhus University Hospital, Denmark. Controls will be healthy volunteers of cancer-free participants matched on age and gender.

Description

Inclusion Criteria:

• Confirmed diagnosis of melanoma and scheduled for ICI treatment at Aarhus University Hospital (AUH), Denmark. The healthy control group will consist of an age- and gender- matched sample of participants.

Exclusion Criteria:

• Previous treatment with immunotherapy
• Neurodegenerative diseases (dementia etc.)
• Substance abuse
• Known progressive psychiatric diseases (e.g., Schizophrenia)
• Other confirmed diagnoses with underlying cognitive impairment
• Insufficient Danish proficiency

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cancer patients with melanoma; Forty seven cancer patients with melanoma included prior to treatment with ICI.
Healthy controls; Fifthy three age- and gender- matched healthy controls.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Attention	Changes in attention as measured with WAIS-IV The Digit Span Forwards (scores with a minimum of 0 points to a maximum of 16 points - higher scores mean a better outcome)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Attention	Changes in attention as measured with Paced Auditory Serial Addition Test (scores ranging from a minimum of 0 and a maximum of 60 with higher scores indicating a better outcome)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Processing Speed	Changes in processing speed as measured with WAIS-IV The Digit Symbol coding (scores ranging from a minimum of 0 and a maximum of 135 with higher scores indicating a better outcome)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Processing Speed	Changes in processing speed as measured with Trail Making Test A (outcome is time in seconds)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Working memory	Changes in working memory as measured with WAIS-IV The Digit Span Backwards (scores with a minimum of 0 points to a maximum of 16 points - higher scores mean a better outcome)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Working memory	Changes in working memory as measured with WAIS-IV The Digit Span Ranking (scores with a minimum of 0 points to a maximum of 16 points - higher scores mean a better outcome)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Learning and memory	Changes in learning and memory as measured with the Hopkins Verbal Learning Test - Revised (part 1 include a minimum score of 0 and a maximum score of 36 with higher score indicating a better outcome, part 2 include a minimum score of 0 and a maximum score of 12 with higher scores indicating better outcomes)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Learning and memory	Changes in learning and memory as measured with Brief Visuospatial Memory Test - Revised (part 1 include a minimum score of 0 and a maximum score of 18 with a higher score indicating a better outcome, part 2 include a minimum score of 0 and a maximum score of 6 with higher scores indicating better outcomes)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Visuospatial ability	Changes in visuospatial ability as measured with WAIS-IV Matrix Reasoning (scores with a minimum of 0 and a maximum of 26 with higher scores indicating better outcomes)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Verbal fluency	Changes in verbal fluency as measured with the Controlled Oral Word Association Test, letter and animal (as many words as possible, more words indicating a better outcome. No maximum value)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Executive function	Changes in executive function as measured with the Trail Making Test B (outcome is time in seconds)	Baseline, and week 8, 24 and 12 weeks after completed treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer-related fatigue	Changes in fatigue severity as measured with The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT fatigue) scale (range from 0 to 52. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Sleep quality	Changes in sleep quality as measured with the Insomnia Severity Index (ISI) (scores ranging from a minimum of 0 and a maximum of 28 with higher scores indicating higher levels of insomnia)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Sleep quality	Changes in sleep quality as measured with the Pittsburgh Sleep Quality Index (PSQI) (scores ranging form a minimum of 0 indicating no difficulty and a maximum of 21 indicating severe difficulties in all areas related to sleep)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Perceived cognitive functioning	Changes in perceived cognitive functioning as measured with The Patient Assessment of Own Functioning Inventory (PAOFI) (outcome is scores ranging from a minimum of 35 to a maximum of 210)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Depression/Anxiety	Changes in depression/anxiety as measured with the Hospital Anxiety and Depression Scale (HADS) (range from a minimum score of 0 to a maximum score of 21 in which a higher scores mean higher levels of depression/anxiety)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Sickness behavior	Changes in subjective sickness behavior as measured with the Sickness Questionnaire (SicknessQ) (scores ranging from a minimum of 0 and a maximum of 30 with higher scores indicating worse outcome)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Health-related quality of life	Changes in health-related quality of life as measured with The European Organization for Research and Treatment of Cancer, Quality of Life questionnaire for cancer patients (EORTC QLQ-C30) (all of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Brain grey matter	Changes in brain grey matter as measured with T1-weighted MRI	Baseline and week 24.
Brain white matter	Changes in brain white matter as measured with T1-weighted MRI	Baseline and week 24.
Moderator: genotype	Genotype of COMT and APOE4 Genotype of COMT	Baseline
Inflammatory immune markers	TNF-α, IL-6, IL-8, IL-21, CRP, IP-10 and MCP-1 extracted from blood samples	Baseline, and week 8, 24 and 12 weeks after completed treatment

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: University of Aarhus

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: September 16, 2020
• First Submitted That Met QC Criteria: September 24, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): December 6, 2024
• Last Update Submitted That Met QC Criteria: December 4, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Melanoma; Immune Checkpoint Inhibitors; Cognitive Dysfunction; Cancer-related Symptoms
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neurocognitive Disorders; Cognition Disorders; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Cognitive Dysfunction; Inflammation; Melanoma; Illness Behavior
• Other Study ID Numbers: 2016-051-000001-1730

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No