The Cohort for Patient-reported Outcomes, Imaging and Trial Inclusion in Metastatic BRAin Disease (COIMBRA) (COIMBRA)

• ClinicalTrials.gov Identifier: NCT05267158
• Recruitment Status: Recruiting
• First Posted: March 4, 2022
• Last Update Posted: September 6, 2022
• Sponsor: UMC Utrecht
• Information provided by (Responsible Party): Joost J.C. Verhoeff, UMC Utrecht

Study Description

Brief Summary:

The incidence of brain metastases is expected to increase because of better treatments of primary tumours. Novel diagnostic and therapeutic techniques are continuously being developed, all of which need thorough evaluation before they can be implemented in clinical routine. Randomized Controlled Trials are the gold standard to do so, but they have shown many challenges, especially when applied in a cancer setting.

.The 'cohort multiple Randomized Controlled Trial (cmRCT)' design is a promising design for multiple (simultaneous) randomized evaluations of experimental interventions, with potential for increased recruitment, comparability and long-term outcomes as a standard. This design will speed up the process of translating treatment innovations to the daily clinic.

Condition or disease
Brain Metastases, Adult; Brain Neoplasms, Adult, Malignant

Detailed Description:

The COIMBRA cohort is a prospective cohort, which will serve as a facility for efficient, systematic and simultaneous evaluation of new interventions and MRI sequences and prospective outcome studies (including prediction modelling).

COIMBRA patients will be followed prospectively and information on survival, symptoms, QoL (patient and caregiver), cognition, toxicity and daily functioning in relation to treatment will be collected prospectively.

Patients will receive the regular optimal clinical care according to the current guidelines when not participating in cmRCT's.

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 1000 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 3 Years
• Official Title: The Cohort for Patient-reported Outcomes, Imaging and Trial Inclusion in Metastatic BRAin Disease (COIMBRA)
• Actual Study Start Date: April 26, 2019
• Estimated Primary Completion Date: May 1, 2024
• Estimated Study Completion Date: May 1, 2026

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Survival [ Time Frame: Through study completion, an average of 1 year ]
   Survival of participating patients will be recorded using the follow up questionnaires (returned by family members) or are derived from the Municipal Personal Records Database (in Dutch: Basisregistratie Personen (BRP))
2. Time and Type of re-intervention [ Time Frame: Through study completion, an average of 1 year ]
   Re-intervention (re-irradiation, surgery, other); Development of neurological symptoms; Development of new metastases.
3. Change in toxicity after radiotherapy [ Time Frame: Through study completion, an average of 1 year ]
   The toxicity will be reported by using the serious adverse event (SAE) questionnaire, every 6 months
4. Technical and treatment data [ Time Frame: Through study completion, an average of 1 year ]

   Dose, fractions and technique of radiotherapy. All other planned and/or received treatment for brain metastases and primary tumour (i.e. systemic therapy, surgery, radiotherapy), and the characteristics there of (type, dose, duration, awake surgery, extent of surgery, complications)

   - Use of epileptic drugs, including type and dose

Secondary Outcome Measures :

1. Change in patient reported outcomes; general quality of life [ Time Frame: Through study completion, an average of 1 year ]

   General quality of life will be reported by the questionnaires named C30 and EQ-5D. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is the instrument most frequently used to measure quality of life in cancer patients, whereas the EQ-5D is widely used to measure and evaluate general health status.

   Baseline, at 1 month, 3 months, and every subsequent 3 months, after initial radiotherapy is completed. Both the total score of the questionnaires and the individual questions are used in which we look at the difference between the measurement moments.

2. Change in patient reported outcomes; cancer related fatigue [ Time Frame: Through study completion, an average of 1 year ]

   Cancer related fatigue is measured by using the MFI-20 questionnaire. The MFI-20 is a 20-item self-report instrument designed to measure fatigue. It covers the following dimensions: general fatigue, physical fatigue, reduced activity, reduced motivation and mental fatigue. The instrument was used in a Dutch and Scottish sample of cancer patients receiving radiotherapy

   Baseline, at 1 month, 3 months, and every subsequent 3 months, after initial radiotherapy is completed. Both the total score of the questionnaires and the individual questions are used in which we look at the difference between the measurement moments.

3. Change in patient reported outcomes; depression and anxiety [ Time Frame: Through study completion, an average of 1 year ]

   Cancer related depression and anxiety is reported by the HADS. The Hospital Anxiety and Depression Scale (HADS) is a self-assessment questionnaire that has been found to be a reliable instrument for detecting states of anxiety and depression in the setting of hospital outpatient clinic. The HADS questionnaire has seven items each for depression and anxiety subscales. Scoring for each item ranges from zero to three, with three denoting highest anxiety or depression level. A total subscale score of >8 points out of a possible 21 denotes considerable symptoms of anxiety or depression.

   Baseline, at 1 month, 3 months, and every subsequent 3 months, after initial radiotherapy is completed. Both the total score of the questionnaire and the individual questions are used in which we look at the difference between the measurement moments.

4. Change in patient reported outcomes; disease-specific symptoms of brain metastases and (adverse) effects of their treatment [ Time Frame: Through study completion, an average of 1 year ]

   Disease-specific symptoms of brain metastases and (adverse) effects of their treatment are measured by a combination of questionnaires: BN20 and CFQ. The BN20 scoring transforms 20 questions into 11 scales to assess neurological deficits (visual disorder, motor dysfunction, communication deficit), future uncertainty, and disease- and treatment-related symptoms.

   The Cognitive Failures Questionnaire (CFQ) is used in ergonomics research to measure behavioural problems associated with attentiveness and memory in everyday life.

   Baseline, at 1 month, 3 months, and every subsequent 3 months, after initial radiotherapy is completed.Both the total scores of each neurological deficit and cognitive failure and the individual questions are used in which we look at the difference between the measurement moments.

5. Change in caregiver reported outcomes: general quality of life [ Time Frame: Through study completion, an average of 1 year ]

   General quality of life will be reported by the questionnaire EQ-5D. The EQ-5D is widely used to measure and evaluate general health status.

   Baseline, at 1 month, 3 months, and every subsequent 3 months, after initial radiotherapy of the patient is completed. Both the total score of the questionnaire and the individual questions are used in which we look at the difference between the measurement moments.

6. Change in caregiver reported outcomes: depression and anxiety [ Time Frame: Through study completion, an average of 1 year ]

   Depression and anxiety is reported by the HADS. The Hospital Anxiety and Depression Scale (HADS) is a self-assessment questionnaire that has been found to be a reliable instrument for detecting states of anxiety and depression in the setting of hospital outpatient clinic. The HADS questionnaire has seven items each for depression and anxiety subscales. Scoring for each item ranges from zero to three, with three denoting highest anxiety or depression level. A total subscale score of >8 points out of a possible 21 denotes considerable symptoms of anxiety or depression.

   Baseline, at 1 month, 3 months, and every subsequent 3 months, after initial radiotherapy of the patient is completed. Both the total score of the questionnaire and the individual questions are used in which we look at the difference between the measurement moments.

7. Change in the caregiver burden [ Time Frame: Through study completion, an average of 1 year ]

   The Caregiver Strain Index (CSI) is a tool that can be used to quickly identify families with potential caregiving concerns. It is a 13-question tool that measures strain related to care provision. There is at least one item for each of the following major domains: Employment, Financial, Physical, Social and Time. Positive responses to seven or more items on the index indicate a greater level of strain. This instrument can be used to assess individuals of any age who have assumed the role of caregiver for an older adult.

   Baseline, at 1 month, 3 months, and every subsequent 3 months, after initial radiotherapy of the patient is completed. Both the total score of the questionnaire and the individual questions are used in which we look at the difference between the measurement moments.

8. Patients coping and personality [ Time Frame: Baseline ]
   Patients are asked to fill out the Utrechtse Coping Lijst (UCL) and the NEO Five-Factor Inventory (NEO-FFI)
9. Caregiver coping and personality [ Time Frame: Baseline ]
   Caregivers are asked to fill out the Utrechtse Coping Lijst (UCL) and the NEO Five-Factor Inventory (NEO-FFI)
10. Neurocognitive functioning [ Time Frame: We are testing this twice: once before radiotherapy and 3 months after radiotherapy ]

    The neuro cognitive assessment (NCA) tests that focus on the specific cognitive domains that are most sensitive to the effects of brain irradiation are used for measuring the neurocognitive functioning.

    The following domains are tested: general cognitive functioning, memory, language, executive functioning, attention, psychomotor speed, fine motor coordination, visuoconstruction, visuoperception, and social cognition. The test battery takes a maximum of 90 minutes to administer and is based upon international standards

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

All patients who are referred to the Department of Radiotherapy for treatment of brain metastases or for prophylactic cranial irradiation (PCI) will be asked to participate in this cohort study.

Criteria

Inclusion Criteria:

• Age ≥ 18 years;
• Either radiographic and/or histologic proof of metastatic brain disease, or eligible for prophylactic cranial irradiation;
• Referred to the Department of Radiotherapy for cranial irradiation.

Exclusion Criteria:

• Mental disorder or cognitive dysfunction that hinder the patient's ability to understand the informed consent procedure and/or study details;
• Patients with severe psychiatric disorders;
• Inability to understand the Dutch language.

Contacts and Locations

Contacts

Contact: Joost JC Verhoeff, MD, PhD; +31-88-7564393; j.j.c.verhoeff-10@umcutrecht.nl

Contact: Fia F Cialdella; +31631118339; f.cialdella@umcutrecht.nl

Locations

Netherlands

University Medical Center Utrecht; Recruiting

Utrecht, Netherlands, 3508GA

Contact: Joost JC Verhoeff, MD, PhD +31-88-7564393 j.j.c.verhoeff-10@umcutrecht.nl

Contact: Fia F Cialdella, MD +31631118339 f.cialdella@umcutrecht.nl

Sub-Investigator: Fia F Cialdella, MD

Principal Investigator: Joost JC Verhoeff, MD, PhD

Sponsors and Collaborators

UMC Utrecht

Investigators

• Principal Investigator: Joost JC Verhoeff, MD, PhD; UMC Utrecht

More Information

Additional Information:

Coimbra Cohort (in Dutch) 

• Responsible Party: Joost J.C. Verhoeff, Principal Investigator, Radiation Oncologist, UMC Utrecht
• ClinicalTrials.gov Identifier: NCT05267158
• Other Study ID Numbers: NL67206.041.18
• First Posted: March 4, 2022
• Last Update Posted: September 6, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Joost J.C. Verhoeff, UMC Utrecht:

radiotherapy (RT); QoL,Quality of life; Neurocognition; Brain metastases; Cranial irradiation; Neoplasm metastasis; Prognosis; Survival; Prospective

Additional relevant MeSH terms:

Neoplasm Metastasis; Brain Neoplasms; Brain Diseases; Neoplasms; Neoplastic Processes; Pathologic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Central Nervous System Diseases; Nervous System Diseases