Longitudinal Neurocognitive, Psychosocial and Health-related Quality of Life Assessment in Advanced Cancer Survivors Treated With Immunotherapy and the Efficacy of Integrative Neurocognitive Remediation Therapy

Quality of Life Clinical Trial

— CognIT  

Official title:

Longitudinal Neurocognitive, Psychosocial and Health-related Quality of Life Assessment in Advanced Cancer Survivors Treated With Immunotherapy and the Efficacy of Integrative Neurocognitive Remediation Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05667857
• Other study ID #: 2022-BN-001
• Status: Recruiting
• Phase: N/A
• Start date: July 13, 2022
• Est. completion date: December 2033

Study information

• Verified date: December 2022
• Source: Universitair Ziekenhuis Brussel
• Contact: Nathalie Vanlaer, MSc
• Phone: +32(0)24763979
• Email: nathalie.vanlaer[@]uzbrussel.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Since 2010, the field of immunotherapy has grown substantially, leading to a growing population of long-term cancer survivors treated with immunotherapy. Since cancer survivorship in immunotherapy is an emerging field, to date not much is known about psychosocial and neurocognitive survivorship-related issues in advanced cancer survivors treated with immunotherapy. Preliminary findings indicated significant psychosocial and cognitive problems in survivors of advanced melanoma persist after treatment with immunotherapy. The objective for this project is twofold. First, the investigators want to longitudinally identify survival-related problems in survivors of advanced cancer treated with immunotherapy. The second goal is to identify the efficacy of an Integrative Neuro-Cognitive Remediation Therapy (INCRT) program. The investigators will focus on the following outcomes: (1) Psychosocial consequences, such as emotional complaints, fatigue, fear of recurrence, (2) neurocognitive functioning, and (3) health-related quality of life. The INCRT combines personalized computerized cognitive training and neurocognitive strategy training, with group sessions of exercise, mindfulness, Acceptance and Commitment Therapy, and cognitive behavioral therapy. We will have three cohorts: - Cohort 1: advanced cancer survivors treated with immunotherapy - Cohort 2: cancer survivors treated with cancer therapy of any kind (excluded immunotherapy), and who have subjective complaints and/or objective cognitive impairment - Cohort 3: cancer survivors of a central nervous system (CNS) tumor, who do not have active disease in the CNS, and who have subjective complaints and/or objective cognitive impairment In the first part of the study, survival-related problems will be evaluated in cohort 1, in a longitudinal manner by means of a semi-structured interview at baseline, various questionnaires and a computerized neuropsychological test battery. In the second part of the study, patients of cohort 1, 2 and 3 with subjective or objective cognitive dysfunction can follow the INCRT program. The efficacy of the INCRT is evaluated through a pre-INCRT and post-INCRT evaluation. This evaluation consist of several questionnaires and neuropsychological tests. Long-term efficacy will be evaluated by a follow-up evaluation six months after completion of the INCRT program.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2033
• Est. primary completion date: November 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Non-intervention group:

• Provision of written informed consent
• Diagnosed with advanced cancer of any type
• Initiated immunotherapy (Anti-PD1, Anti-PDL1, CTLA-4, …) at least one year ago
• Have a confirmed normalization on whole-body 18F-FDG PET
• English, Dutch or French-speaking

2. Integrative neurocognitive remediation therapy group:

• Provision of written informed consent
• Objective cognitive impairment and/or subjective cognitive complaints
• Confirmed normalization on whole-body 18F-FDG PET for patients (cohort 1)
• Disease-free (cohort 2) or no active disease for patients with CNS tumors (cohort 3)
• Having received a cancer therapy of any kind
• Having ended cancer treatment (immunotherapy, chemotherapy, radiotherapy, surgery, …) with an exception of ongoing adjuvant hormone therapy
• Dutch or French speaking

Exclusion Criteria:

• severe co-morbid non cancer-related psychiatric disorders such as psychosis, obsessive compulsive disorders, eating disorders etc., patients with cognitive impairment related to dementia, and patients that are physically or mentally not able to fill in the questionnaires

Related Conditions & MeSH terms

• Cancer Survivors
• Cognitive Behavioral Therapy
• Cognitive Dysfunction
• Cognitive Remediation
• Immunotherapy
• Neuropsychology
• Psycho-Oncology
• Psychological Distress
• Quality of Life

Intervention

Behavioral:
• Integrative neurocognitive remediation therapy
Integrative Neurocognitive Remediation Therapy is a clinical program of 12 weeks (1 day/week) that combines personalized computerized cognitive training and neurocognitive strategy training, with group sessions of adapted physiotherapy, acceptance and commitment therapy (ACT), cognitive behavioral therapy (CBT) and information sessions on cognition, fatigue, nutrition and physical exercise.

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Brussel	Brussel	Brussels Hoofdstedelijk Gewest
Belgium	University Hospital Brugmann	Brussel	Brussels Hoofdstedelijk Gewest

Sponsors (2)

Lead Sponsor	Collaborator
Universitair Ziekenhuis Brussel	Brugmann University Hospital

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective neurocognitive functioning measured by the COGBAT neuropsychological battery.	To measure neurocognitive functioning (attention, memory and executive functioning), with the computerized neuropsychological test battery COGBAT. This battery gives an overall degree of objective neurocognitive functioning, in addition to the specific test performance per subtest. The test performance will be measured in raw scores and z-scores. This test battery will be repeated during follow-up for the non-intervention group. For the intervention group, the scores will be compared before and after the integrative neurocognitive remediation therapy, and 6 months thereafter. Improvement in test performance after the therapy program, compared to baseline, will indicate efficacy of the integrative neurocognitive remediation therapy program.	Until study completion, with an average of 3 years
Primary	Subjective cognitive complaints measured by the Cognitive Failures Questionnaire.	To measure subjective cognitive functioning as assessed by the Cognitive Failures Questionnaire, values ranging from 0 to 100. Higher values mean more cognitive complaints. This will be repeated during follow-up for the non-intervention group. For the intervention group, the scores will be compared before and after the integrative neurocognitive remediation therapy, and 6 months thereafter. A cut-off score of 44 will be used to define elevated levels of cognitive complaints, a score higher than 54 indicates severe cognitive complaints. Improvement in subjective cognitive complaints after the therapy program, compared to baseline, will indicate efficacy of the integrative neurocognitive remediation therapy program.	Until study completion, with an average of 3 years
Primary	Emotional distress as assessed by the Hospital Anxiety and Depression Scale.	To identify emotional distress, the Hospital Anxiety and Depression Scale will be used, with values ranging from 0 to 42. Higher scores mean more emotional distress. This will be repeated during follow-up for the non-intervention group. For the intervention group, the scores will be compared before and after the integrative neurocognitive remediation therapy, and 6 months thereafter. A cut-off score of 8 will be used to define elevated levels of emotional distress, a score higher than 10 corresponds to moderate emotional distress, a score higher than 14 corresponds to severe emotional distress.	Until study completion, with an average of 3 years
Primary	Fatigue as assessed by Fatigue Severity Scale.	To identify fatigue, the Fatigue Severity Scale will be used. Mean scores will be calculated, leading to a score between 1 and 7. Higher values indicate more fatigue. This will be repeated during follow-up for the non-intervention group. For the intervention group, the scores will be compared before and after the integrative neurocognitive remediation therapy, and 6 months thereafter. A cut-off score of 4 will be used to define elevated levels of fatigue.	Until study completion, with an average of 3 years
Primary	Fear of cancer recurrence as assessed by the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF).	To identify fear of cancer recurrence, the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF). will be used. Values range from 0 to 36 and higher values indicate more fear of cancer recurrence. This will be repeated during follow-up for the non-intervention group. For the intervention group, the scores will be compared before and after the integrative neurocognitive remediation therapy, and 6 months thereafter. A cut-off score of 13 will be used to define significant fear of cancer recurrence. A score higher than 15 equals clinically significant fear of cancer recurrence, a score higher than 21 equals a pathological fear of cancer recurrence.	Until study completion, with an average of 3 years
Primary	Health-related quality of life as assessed by the EORTC Quality of Life Core 30 Questionnaire.	To measure health-related quality of life, the EORTC Quality of Life Questionnaire (EORTC-QLQ-C30) will be used. Transformed scores range between 0 and 100, higher scores indicate better health-related quality of life. This will be repeated during follow-up for the non-intervention group. For the intervention group, the scores will be compared before and after the integrative neurocognitive remediation therapy, and 6 months thereafter. The scores will be compared to the Threshold of Clinical Importance, developed by Giesinger et al. (2020). To evaluate change over time, the changes of at least 10 points are regarded, which are supported to be clinically meaningful changes (Snyder et al., 2014).	Until study completion, with an average of 3 years
Secondary	To document baseline demographic data, prior disease history, nature of immunotherapy therapy	To document baseline demographic data, prior disease history, nature of immunotherapy therapy, the investigators will look into the patient medical record and a general questionnaire will be used.	Baseline
Secondary	To measure the feasibility of the implementation in a larger scale of this clinical cognitive rehabilitation program for cancer survivors, as assessed by the resources needed to implement this program.	To explore the feasibility of the implementation in a larger scale of this clinical program will be assessed by the care need of the patients and the possibility to implement the therapy program in other hospitals (resources needed, cost of the program for the patient).	Until study completion, with an average of 3 years
Secondary	To measure the relation between psychological distress, as assessed by the Hospital Anxiety and Depression Scale, and subjective cognitive functioning, as assessed by the Cognitive Failures Questionnaire.	Psychological distress will be measured by the sum scores of the Hospital Anxiety and Depression Scale. Subjective cognitive functioning will be measured by the sum scores of the Cognitive Failures Questionnaire. To measure the relation between the two variables, the investigators will conduct a statistical correlation of these outcomes. The outcome will be a correlation coefficient (r).	Until study completion, with an average of 3 years
Secondary	To measure the relation between psychological distress, as assessed by the Hospital Anxiety and Depression Scale, and objective cognitive functioning, as assessed by the COGBAT neuropsychological battery.	Psychological distress will be measured by the sum scores of the Hospital Anxiety and Depression Scale. Objective cognitive functioning will be measured by the COGBAT neuropsychological battery. To measure the relation between the two variables, the investigators will conduct a statistical correlation of these outcomes. The outcome will be a correlation coefficient (r).	Until study completion, with an average of 3 years
Secondary	To measure the relation between subjective neurocognitive functioning, as assessed by the Cognitive Failures Questionnaire, and the objective cognitive functioning, as assessed by the COGBAT neuropsychological battery.	Subjective cognitive functioning will be measured by the sum scores of the Cognitive Failures Questionnaire. Objective cognitive functioning will be measured by the COGBAT neuropsychological battery. To measure this relation, the investigators will conduct a statistical correlation of these outcomes. The outcome will be a correlation coefficient (r).	Until study completion, with an average of 3 years
Secondary	To explore the care needs of personalized nutritional advice.	This will be assessed through two open questions asked to the patient, more specifically: 1) if the patient has interest in personalized nutritional advice, 2) what the specific nutritional care need is of the patient.	Until study completion, with an average of 3 years
Secondary	Rumination as assessed by the Brooding items of the Ruminative Response Scale (RRS).	To identify rumination, the Brooding items of the Ruminative Response Scale (RRS) will be used. Values range from 5 to 20, higher values indicate more tendency of 'Brooding', a maladaptive type of rumination. This will be repeated during follow-up for the non-intervention group. For the intervention group, the scores will be compared before and after the integrative neurocognitive remediation therapy, and 6 months thereafter.	Until study completion, with an average of 3 years
Secondary	Visuo-spatial short-term memory measured by the computerized version of the Corsi Block Tapping Test by the Vienna Test System	To measure visuo-spatial memory span, with the computerized version of the Corsi Block Tapping Test by the Vienna Test System. The test performance will be measured in raw scores and z-scores. This will be repeated during follow-up for the non-intervention group. For the intervention group, the scores will be compared before and after the integrative neurocognitive remediation therapy, and 6 months thereafter.	Until study completion, with an average of 3 years
Secondary	Verbal long-term memory measured by the California Verbal Learning Test	To measure verbal long-term memory measured by the California Verbal Learning Test. This will be tested only in the intervention group, i.e. the patients that will follow the integrative neurocognitive remediation therapy. It will be repeated after completion of the therapy program and six months thereafter. The test performance will be measured in raw scores and z-scores.	Until study completion, with an average of 3 years
Secondary	Information processing speed measured by the WAIS-IV Symbol Search and Coding	To measure information processing speed measured by the WAIS-IV Symbol Search and Coding. This will be tested only in the intervention group, i.e. the patients that will follow the integrative neurocognitive remediation therapy. It will be repeated after completion of the therapy program and six months thereafter. The test performance will be measured in raw scores and Weschler subscale scores. The Weschler subscale scores range from 0-20 and have a mean of 10.	Until study completion, with an average of 3 years
Secondary	Verbal short-term memory measured by the WAIS-IV Digit Span Forwards	To measure verbal short-term memory by the WAIS-IV Digit Span Forwards. This will be tested only in the intervention group, i.e. the patients that will follow the integrative neurocognitive remediation therapy. It will be repeated after completion of the therapy program and six months thereafter. The test performance will be measured in raw scores and z-scores.	Until study completion, with an average of 3 years
Secondary	Working memory measured by the WAIS-IV Digit Span Backwards	To measure working memory by the WAIS-IV Digit Span Backwards. This will be tested only in the intervention group, i.e. the patients that will follow the integrative neurocognitive remediation therapy. It will be repeated after completion of the therapy program and six months thereafter. The test performance will be measured in raw scores and z-scores.	Until study completion, with an average of 3 years
Secondary	Anxiety as assessed by the State-Trait Anxiety Inventory	Anxiety will be measured by the State-Trait Anxiety Inventory. This will be tested only in the intervention group, i.e. the patients that will follow the integrative neurocognitive remediation therapy. It will be repeated after completion of the therapy program and 6 months thereafter. Values range from 20 to 80. Higher values indicate more anxiety. STAI scores classified as "no or low anxiety" (20-37), "moderate anxiety" (38-44), and "high anxiety" (45-80).	Until study completion, with an average of 3 years
Secondary	Self-esteem as assessed by the Rosenberg Self-Esteem Scale.	Self-esteem will be measured by the Rosenberg Self-Esteem Scale. This will be tested only in the intervention group, i.e. the patients that will follow the integrative neurocognitive remediation therapy. It will be repeated after completion of the therapy program and 6 months thereafter. Values range from 0 to 30. Higher values indicate a higher self-esteem. Scores between 15 and 25 are within normal range; scores below 15 correspond to low self-esteem.	Until study completion, with an average of 3 years
Secondary	Tendency for procrastination as assessed by the Pure Procrastination Scale.	Tendency for procrastination will be measured by the Pure Procrastination Scale. This will be tested only in the intervention group, i.e. the patients that will follow the integrative neurocognitive remediation therapy. It will be repeated after completion of the therapy program and six months thereafter. Values range from 11 to 55. Higher values indicate more tendency for procrastination. A score lower than 28 indicate a low level of procrastination, a score between 28-39 indicate a moderate level of procrastination, and a score higher than 39 indicate a high level of procrastination.	Until study completion, with an average of 3 years
Secondary	Metacognition as assessed by the Metacognition Questionnaire.	Metacognition will be measured by the Metacognition Questionnaire. This will be tested only in the intervention group, i.e. the patients that will follow the integrative neurocognitive remediation therapy. It will be repeated after completion of the therapy program and six months thereafter. Values range from 30 to 120. Higher values indicate more metacognitive beliefs.	Until study completion, with an average of 3 years
Secondary	Tendency for perfectionism as assessed by the Frost Multidimensional Perfectionism Scale.	Tendency for perfectionism will be measured by the Frost Multidimensional Perfectionism Scale. This will be tested only in the intervention group, i.e. the patients that will follow the integrative neurocognitive remediation therapy. It will be repeated after completion of the therapy program and six months thereafter. Values range from 35 to 210, higher values indicate more tendency for perfectionism.	Until study completion, with an average of 3 years
Secondary	Post-traumatic stress disorder symptoms as assessed by the PTSD checklist for DSM-5 (PCL-5).	To identify post-traumatic stress disorder (PTSD) symptoms, the PTSD checklist for DSM-5 (PCL-5) will be used. Values range from 0 to 80, and higher values indicate more symptoms of post-traumatic stress. This will be repeated during follow-up for the non-intervention group. For the intervention group, the scores will be compared before and after the integrative neurocognitive remediation therapy, and 6 months thereafter. A cut-off score of 33 indicates PTSD.	Until study completion, with an average of 3 years
Secondary	Subjective cognitive complaints measured by the cognitive functioning subscale of the EORTC QLQ-C30.	To measure subjective cognitive functioning as assessed by the EORTC QLQ-C30, cognitive functioning subscale. Transformed scores range from 0 to 100, with higher scores meaning better cognitive functioning. This will be repeated during follow-up for the non-intervention group. For the intervention group, the scores will be compared before and after the integrative neurocognitive remediation therapy, and 6 months thereafter. The scores will be compared to the Threshold of Clinical Importance, developed by Giesinger et al. (2020). To evaluate change over time, the changes of at least 10 points are regarded, which are supported to be clinically meaningful changes (Snyder et al., 2014).	Until study completion, with an average of 3 years