Neoplasms

Symptoms and General Pathology

All Conditions

Nervous System Diseases

Behaviors and Mental Disorders

Neoplasm Metastasis

Brain Diseases

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Central Nervous System Diseases

Quality of Life

Joost JC Verhoeff, MD, PhD

Fia F Cialdella

Fia F Cialdella, MD

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.

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.

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

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))

Re-intervention (re-irradiation, surgery, other); Development of neurological symptoms; Development of new metastases.

The toxicity will be reported by using the serious adverse event (SAE) questionnaire, every 6 months

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

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.

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.

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.

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.

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.

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.

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.

Patients are asked to fill out the Utrechtse Coping Lijst (UCL) and the NEO Five-Factor Inventory (NEO-FFI)

Caregivers are asked to fill out the Utrechtse Coping Lijst (UCL) and the NEO Five-Factor Inventory (NEO-FFI)

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

UMC Utrecht

Principal Investigator, Radiation Oncologist

Skin and Connective Tissue Diseases

Rare Diseases

Glioma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Dermatitis, Phototoxic

Neoplasm, Residual

Dermatitis

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Dermatitis, Irritant

Dermatitis, Contact

Skin Diseases

Photosensitivity Disorders

Skin Diseases, Eczematous

Neuroepithelioma

Central Nervous System Depressants

All Drugs and Chemicals

Pharmaceutical Solutions

Dermatologic Agents

Anesthetics

Aminolevulinic Acid

Photosensitizing Agents

Patients with malignant gliomas undergoing neurosurgical procedures using 5-aminolevulinic acid (5-ALA)-based photodynamic therapy

Gliolan® is presented as a powder for oral solution in 60 ml colorless glass vials and is administered orally three hours (range 2-4 hours) before anaesthesia. One bottle contains 1.17 g of 5-aminolevulinic acid (5-ALA), corresponding to 1.5 g 5-aminolevulinic acid hydrochloride (5-ALA HCl). The recommended dose is 20 mg 5-ALA HCl per kilogram body weight. One ml of reconstituted solution contains 23.4 mg of 5-ALA, corresponding to 30 mg 5-ALA HCl.

5-Aminolevulinic Acid (5-ALA) Gliolan®

During the surgical exploration of the glioma, the neurosurgeon will attempt to identify the mass. The location of the tumor will be assessed using the blue-light filtered microscope. A biopsy of the fluorescent region will be taken to confirm the glioma subtype. The tumor will then be maximally resected.

Fluorescence-Guided Surgery using 5-aminolevulinic acid (5-ALA)

Alberto Valarezo Chuchuca, MD

The goal of this observational study is to evaluate disease-free survival (DFS) in patients with malignant gliomas undergoing neurosurgical procedures using 5-aminolevulinic acid (5-ALA)-based photodynamic therapy

The investigators are proposing a study that provides descriptive understanding of patients with High-Grade Gliomas in Ecuador. The primary objective of this pilot study is to lay the foundations for the development of a multicenter registry patients with malignant gliomas undergoing neurosurgical procedures using 5-aminolevulinic acid (5-ALA)-based photodynamic therapy, which will provide high-quality real data and serve as a basis for the application to future projects and elaboration of public policies in the medium and long term.

5-Aminolevulinic Acid (5-ALA) Gliolan®: Usage Increase Proposal for Neurosurgical Procedures in High-Grade Gliomas

Disease-Free-Survival calculates the time from treatment until the recurrence of disease or death after undergoing Fluorescence-Guided Surgery using 5-aminolevulinic acid (5-ALA)

Overall survival is defined as time from initiation to death of any cause

The questionnaire provides an additional set of disease-specific questions pertaining to brain neoplasms. It consists of 46 items that refer to general issues of quality of life and specific to tumor location. Possible scores range from 0 to 108, with higher scores indicating better quality of life.

The average length of stay in hospitals is often used as an indicator of efficiency. The ALOS refers to the average number of days that patients spend in hospital after surgery. It is calculated by dividing the number of bed-days by the number of discharges after procedure. Average length of stay range from 1 day to 4.5 days. Longer than average stays are usually a symptom of poor communication, quality of care, and effectiveness of treatment.

Sociedad de Lucha Contra el Cáncer del Ecuador

Glioblastoma

Astrocytoma

Antineoplastic Agents

Niraparib

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Participants will receive niraparib 200 mg orally once daily starting on Day 1 of RT. Following completion of RT, participants will continue niraparib adjuvant therapy orally once daily on Days 1 to 28 of each 28-day cycle until progression by BICR

Participants randomized to the comparator arm (Arm B) will receive SOC TMZ 75 mg/m2 orally once daily with RT starting on Day 1 of RT. Following completion of RT, participants will complete a 4-week rest period, and then receive adjuvant TMZ 150 to 200 mg/m2 orally once daily on Days 1 to 5 of each 28-day cycle until progression by BICR or for a maximum of 6 cycles.

Study Navigator

Nader Sanai, MD

The goal of this Phase 3 clinical trial is to compare the efficacy of niraparib versus temozolomide (TMZ) in adult participants with newly-diagnosed, MGMT unmethylated glioblastoma multiforme (GBM). The main questions it aims to answer are:

Does niraparib improve progression-free survival (PFS) compared to TMZ?

Does niraparib improve overall survival (OS) compared to TMZ?

Participants will be randomly assigned to one of two treatment arms: niraparib or TMZ.

* study drug (Niraparib) or
* comparator drug (Temozolomide - which is the standard approved treatment for MGMT unmethylated glioblastoma).

The study medication will be taken daily while receiving standard of care radiation therapy (RT) for 6-7 weeks.

Participants may continue to take the niraparib or TMZ adjuvantly as long as the cancer does not get worse or completion of 6 cycles of treatment (TMZ). A total of 450 participants will be enrolled in the study.

Participants' tasks will include:

* Complete study visits as scheduled
* Complete a diary to record study medication

Blinded Independent Central Review is composed of independent radiologists and will be utilized to assess progression of disease

A Study Comparing Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma

A Phase 3, Open-label, Randomized 2-arm Study Comparing the Clinical Efficacy and Safety of Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma

Progression-free survival, defined as the time from the date of randomization to the date of first disease progression per RANO 2.0 by BICR assessment or death from any cause, whichever occurs first.

Overall survival, defined as the time from the date of randomization to the date of death due to any cause.

Percentage of patients who achieved confirmed complete response or confirmed partial response to treatment evaluated using RANO 2.0 by BICR.

EORTC QLQ-C30 is a validated questionnaire to assess overall health-related quality of life in participants with cancer.

EORTC QLQ-BN20 is a clinically valid and useful tool for assessing disease- and treatment-specific symptoms in brain neoplasm participants.

Hopkins Verbal Learning Test is designed to evaluate memory. It requires participants to memorize a list of 12 items for 3 consecutive tests (recall), to identify the same 12 items from a list of semantically related or unrelated items (recognition), and to recall the same 12 items after a 15-minute delay (delayed recall).

The Controlled Oral Word Association Test is designed to evaluate verbal fluency. It requires participants to name words beginning with a specific letter with increasing associated activity, in 3 one-minute periods.

The Trail Making Test Part A is designed to evaluate visual motor scanning speed, and the Trail Making Test Part B is designed to evaluate executive function. These tests require participants to connect circles in numerical (Part A) or alternating numerical and alphabetical sequence (Part B) within a timed interval of less than 5 minutes for each test.

Treatment discontinuations, dose interruptions, and dose reductions

The PRO-CTCAE is a patient-reported outcome measure developed to evaluate symptomatic toxicity in patients on cancer clinical trials.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Cohort for Patient-reported Outcomes, Imaging and Trial Inclusion in Metastatic BRAin Disease (COIMBRA)	NCT05267158	Brain Metastase... Brain Neoplasms...		18 Years -	UMC Utrecht
The Cohort for Patient-reported Outcomes, Imaging and Trial Inclusion in Metastatic BRAin Disease (COIMBRA)	NCT05267158	Brain Metastase... Brain Neoplasms...		18 Years -	UMC Utrecht
5-Aminolevulinic Acid (5-ALA) Gliolan®: Usage Increase Proposal for Neurosurgical Procedures in High-Grade Gliomas	NCT05850377	High Grade Glio... Glioma Glioma, Maligna... Neoplasms, Neur... Neuroectodermal... Photosensitizin... Neoplasm Malign... Brain Neoplasms... Central Nervous... Brain Tumor Tumour, Residua...	5-Aminolevulini... Fluorescence-Gu...	18 Years - 75 Years	Sociedad de Lucha Contra el Cáncer del Ecuador
A Study Comparing Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma	NCT06388733	Glioblastoma GBM Brain Neoplasms... Brain Tumor	Niraparib Temozolomide	18 Years -	NeuroTrials, LLC
The Cohort for Patient-reported Outcomes, Imaging and Trial Inclusion in Metastatic BRAin Disease (COIMBRA)	NCT05267158	Brain Metastase... Brain Neoplasms...		18 Years -	UMC Utrecht

Spots Global Cancer Trial Database for brain neoplasms, adult, malignant