WHOle Brain Irradiation or STEreotactic Radiosurgery for Five or More Brain Metastases (WHOBI-STER)

Quality of Life Clinical Trial

— WHOBI-STER  

Official title:

WHOle Brain Irradiation and STEreotactic Radiosurgery for Five or More Brain Metastases (WHOBI-STER): a Prospective Comparative Study of Neurocognitive Outcomes, Level of Autonomy in Daily Activities and Quality of Life

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04891471
• Other study ID #: 70/2020/CECT2
• Status: Recruiting
• Phase: N/A
• Start date: September 15, 2020
• Est. completion date: September 15, 2025

Study information

• Verified date: January 2023
• Source: Mediterranean Institute of Oncology
• Contact: Gianluca Ferini
• Phone: +393311341117
• Email: gianluca.ferini[@]grupposamed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This work aims to evaluate neurocognitive performance, daily activity and quality of life and local control among patients with brain metastasis (MBM) ≥ 5 due to solid tumors treated with Stereotactic RadioSurgery (SRS) or Whole Brain RadioTherapy (WBRT). This multicentric randomised controlled trial will be conducted at the Fondazione IOM (Viagrande) in collaboration with REM (Viagrande), Hospital G. Martino (Messina) and Hospital Civico ARNAS (Palermo). It will involve, within 5 years starting from 15 September 2020, the enrollment of 100 patients (50 for each arm) with MBM ≥ 5, age ≥ 18 years, Karnofsky Performance Status (KPS) ≥ 70, life expectancy > 3 months, histological confirmation of primary tumor, with controlled or controllable extracranial disease, baseline Montreal Cognitive Assessment (MoCA) of 20/30, Barthel Activities of Daily Living score 90/100, to be subjected to SRS on each brain lesion by LINAC with monoisocentric technique and non-coplanar arcs (experimental arm) or to WBRT (control arm). The primary endpoints are neurocognitive performance, quality of life and autonomy in daily-life activities variations, the first one assessed by Moca Score and Hopkins Verbal Learning Test - Revised, the second one through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL) and Brain Neoplasm (BN-20) questionnaires, the third one through the Barthel Index, respectively. The secondary endpoints are time to intracranial failure, overall survival, retreatments frequency, acute and late toxicities, KPS decrease. It will be considered significant a statistical difference of at least 29% between the two arms (statistical power of 80% with a significance level of 95%). This trial has been approved by the local ethics committee on July 7th 2020 (record 70). Several studies debate what is the predominant factor accountable for the development of neurocognitive decay among patients undergoing brain irradiation for MBM: radiotherapy, especially if extended to the entire brain, or intracranial disease progression? Answer to this question may come from current opportunity, thanks to recent technological advancement, to treat, with significant time savings, improved patient comfort and at the same time minimizing the dose to healthy brain tissue, Multiple Brain Metastasis simultaneously, otherwise attackable only by panencephalic irradiation. The pursuit of a local control rate comparable to that obtainable with WBRT remains the fundamental prerequisite for the aforementioned related assessments.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 15, 2025
• Est. primary completion date: September 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age > 18
• Life expectancy > 3 months
• Brain metastases number = 5
• Primary tumor histologic diagnosis
• Complete Extracranial staging
• Montreal Cognitive Assessment = 20/30
• Barthel Activities of Daily Living = 90/100
• KPS = 70
• Signed Informed Consent

Exclusion Criteria:

• Brain-MRI contraindications
• Contraindications to SRS
• Pregnancy
• Hemorrhagic cerebral disease
• Miliary metastases
• Massive perilesional edema
• Leptomeningeal involvement
• Previous brain irradiation
• Dementia
• Non-solid brain tumor
• Ischaemic event
• Alcohol and/or drugs abuse
• Anxiety and depression
• KPS = 60
• Life expectancy < 3 months

Related Conditions & MeSH terms

• Activities of Daily Living
• Brain Neoplasms
• Neoplasm Metastasis
• Neurocognitive Deficit
• Quality of Life

Intervention

Radiation:
• Stereotactic RadioTherapy
To treat only brain metastasis identified through Magnetic Resonance imaging by means of stereotactic radiotherapy (experimental intervention) to determine if sparing of clinically uninvolved brain implies a better neurocognitive performance, quality of life and level of autonomy in activities of daily living respect to Whole Brain Irradiation (active comparator).
• Whole Brain Irradiation
To irradiate the entire brain, site of at least 5 parenchymal metastasis.

Locations

Country	Name	City	State
Italy	Radiation Oncology Unit - Department of Biomedical, Dental Science and Morphological and Functional Images, University of Messina	Messina
Italy	Radiation Oncology, ARNAS-Civico Hospital	Palermo
Italy	Fondazione Istituto Oncologico del Mediterraneo	Viagrande	Catania
Italy	REM Radiotherapy (parent company of Mediterranean Institute of Oncology)	Viagrande	Catania

Sponsors (3)

Lead Sponsor	Collaborator
Mediterranean Institute of Oncology	University of Messina, University of Palermo

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurocognitive changes detected through Moca Score	To assess how neurocognitive performance changes after SRS/SBRT compared to WBI	Change from Baseline pre-Radiotherapy Neurocognitive Functional Status every three months after treatment through study completion, an average of 1 year
Primary	Changes of Autonomy in daily activities detected through the Barthel Index	To assess how level of autonomy in activities of daily living changes after SRS/SBRT compared to WBI	Change from Baseline pre-Radiotherapy Barthel Index every three months after treatment through study completion, an average of 1 year
Primary	Change in quality of life detected though the EORTC QLQ-C15-PAL questionnaire	To assess how quality of life changes after SRS/SBRT compared to WBI	Change from Baseline pre-Radiotherapy EORTC QLQ-C15-PAL questionnaire every three months after treatment through study completion, an average of 1 year
Primary	Neurocognitive changes detected through Hopkins Verbal Learning Test - Revised	To assess how neurocognitive performance changes after SRS/SBRT compared to WBI	Change from Baseline pre-Radiotherapy Neurocognitive Functional Status every three months after treatment through study completion, an average of 1 year
Primary	Change in quality of life detected though the BN-20 questionnaire	To assess how quality of life changes after SRS/SBRT compared to WBI	Change from Baseline pre-Radiotherapy BN-20 questionnaire every three months after treatment through study completion, an average of 1 year
Secondary	Time to local failure	Time between treatment and cerebral disease progression detected through Magnetic Resonance imaging	every three months after treatment through study completion, an average of 1 year
Secondary	Overall Survival	Time from the first day of treatment to exitus	after treatment completion through study completion, an average of 1 year
Secondary	Re-treatment rate	Difference in needing further subsequent radiotherapy treatment between SRS/SBRT and WBI arms	after first treatment completion through study completion, an average of 1 year
Secondary	Acute Central Nervous System (CNS) toxicities evaluated by means of Radiation Therapy Oncology Group (RTOG)/ European Organization for Research and Treatment of Cancer (EORTC) Radiation Toxicity Grading	Toxicities registered within three months from treatment	from treatment completion until three months later
Secondary	Late Central Nervous System (CNS) toxicities evaluated by means of Radiation Therapy Oncology Group (RTOG)/ European Organization for Research and Treatment of Cancer (EORTC) Radiation Toxicity Grading	Toxicities registered after three months from treatment	from three months after treatment completion through study completion, an average of 1 year
Secondary	Karnofsky Performance Status changing	Evaluation of how patient's performance status modifies after treatment	after treatment completion through study completion, an average of 1 year