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Cognitive Function in Patients Treated for Metastatic Melanoma With Immune Checkpoint Inhibitors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04565769
Recruitment Status : Not yet recruiting
First Posted : September 25, 2020
Last Update Posted : September 29, 2020
Sponsor:
Collaborator:
University of Aarhus
Information provided by (Responsible Party):
Josefine Tingdal Taube, Aarhus University Hospital

Brief Summary:
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.

Condition or disease
Metastatic Melanoma Cognitive Impairment Fatigue Sleep Depression, Anxiety Quality of Life Inflammation Sickness Behavior Cancer-related Cognitive Impairment

Detailed Description:

This controlled prospective observational study will include two groups with a total of 84 participants. A total of 42 patients diagnosed with metastatic melanoma, referred to treatment with ICI will be enrolled in the study and examined prior to treatment with ICI (baseline), at nine weeks following baseline (T2), at 24 weeks following baseline (T3) and at 36 weeks following baseline (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.

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Study Type : Observational
Estimated Enrollment : 84 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Cognitive Function in Patients Treated for Metastatic Melanoma With Immune Checkpoint Inhibitors: A Controlled Prospective Observational Study
Estimated Study Start Date : September 2020
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2023

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Group/Cohort
Cancer patients with metastatic melanoma
Forty two cancer patients with metastatic melanoma included prior to treatment with ICI.
Healthy controls
Forty two age- and gender- matched healthy controls.



Primary Outcome Measures :
  1. Attention [ Time Frame: Baseline, and week 9, 24 and 36 ]
    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)

  2. Attention [ Time Frame: Baseline, and week 9, 24 and 36 ]
    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)

  3. Processing Speed [ Time Frame: Baseline, and week 9, 24 and 36 ]
    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)

  4. Processing Speed [ Time Frame: Baseline, and week 9, 24 and 36 ]
    Changes in processing speed as measured with Trail Making Test A (outcome is time in seconds)

  5. Working memory [ Time Frame: Baseline, and week 9, 24 and 36 ]
    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)

  6. Working memory [ Time Frame: Baseline, and week 9, 24 and 36 ]
    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)

  7. Learning and memory [ Time Frame: Baseline, and week 9, 24 and 36 ]
    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)

  8. Learning and memory [ Time Frame: Baseline, and week 9, 24 and 36 ]
    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)

  9. Visuospatial ability [ Time Frame: Baseline, and week 9, 24 and 36 ]
    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)

  10. Verbal fluency [ Time Frame: Baseline, and week 9, 24 and 36 ]
    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)

  11. Executive function [ Time Frame: Baseline, and week 9, 24 and 36 ]
    Changes in executive function as measured with the Trail Making Test B (outcome is time in seconds)


Secondary Outcome Measures :
  1. Cancer-related fatigue [ Time Frame: Baseline, and week 9, 24 and 36. ]
    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)

  2. Sleep quality [ Time Frame: Baseline, and week 9, 24 and 36. ]
    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)

  3. Sleep quality [ Time Frame: Baseline, and week 9, 24 and 36. ]
    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)

  4. Perceived cognitive functioning [ Time Frame: Baseline, and week 9, 24 and 36. ]
    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)

  5. Depression/Anxiety [ Time Frame: Baseline, and week 9, 24 and 36. ]
    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)

  6. Sickness behavior [ Time Frame: Baseline, and week 9, 24 and 36. ]
    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)

  7. Health-related quality of life [ Time Frame: Baseline, and week 9, 24 and 36. ]
    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.)

  8. Moderator: genotype [ Time Frame: Baseline ]
    Genotype of genes such as COMT and APOE4

  9. Inflammatory immune markers [ Time Frame: Baseline, and week 9, 24 and 36. ]
    TNF-α, IL-6, IL-1β, IL-10, CRP, IL-10, IFNγ and IFNβ extracted from blood samples

  10. Brain grey matter [ Time Frame: Baseline and week 24. ]
    Changes in brain grey matter as measured with T1-weighted MRI

  11. Brain white matter [ Time Frame: Baseline and week 24. ]
    Changes in brain white matter as measured with T1-weighted MRI


Biospecimen Retention:   Samples With DNA
Blood samples


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients diagnosed with metastatic 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.
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of metastatic 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04565769


Contacts
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Contact: Josefine Tingdal T Danielsen, MSc 004528725594 jtd@psy.au.dk
Contact: Robert Zachariae, Prof, DMSc 004587165878 bzach@rm.dk

Locations
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Denmark
Aarhus University Hospital
Aarhus, Denmark, 8200
Sponsors and Collaborators
Aarhus University Hospital
University of Aarhus
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Responsible Party: Josefine Tingdal Taube, Cand.psych., Ph.d.-fellow, Aarhus University Hospital
ClinicalTrials.gov Identifier: NCT04565769    
Other Study ID Numbers: 2016-051-000001-1730
First Posted: September 25, 2020    Key Record Dates
Last Update Posted: September 29, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Josefine Tingdal Taube, Aarhus University Hospital:
Immune Checkpoint Inhibitors
Metastatic Melanoma
Cancer-related Symptoms
Cognitive Dysfunction
Additional relevant MeSH terms:
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Melanoma
Inflammation
Cognitive Dysfunction
Illness Behavior
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pathologic Processes
Cognition Disorders
Neurocognitive Disorders
Mental Disorders