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

NCT04891471 | Unknown

• 1 other identifier: 70/2020/CECT2
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Neurocognitive Deficit; Quality of Life; Activities of Daily Living

Keywords

multiple brain metastasis; neurocognitive decay; whole brain radiotherapy; stereotactic radiosurgery; stereotactic body radiotherapy; quality of life; solid tumor; Activities of Daily Living; best supportive care; palliative radiotherapy

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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 Outcomes (6)

• Time to local failure

  every three months after treatment through study completion, an average of 1 year

• Overall Survival

  after treatment completion through study completion, an average of 1 year

• Re-treatment rate

  after first treatment completion through study completion, an average of 1 year

• 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

  from treatment completion until three months later

• 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

  from three months after treatment completion through study completion, an average of 1 year

Study Arms (2)

SRS/SBRT arm

EXPERIMENTAL

Patients with five or more brain metastasis assigned by randomization to Stereotactic RadioSurgery (SRS) or Stereotactic Body RadioTherapy (SBRT) will be treated with a highly-conformal metastasis-directed single dose between 15 and 24 Gy or fractionated dose (e.g. 27 Gy in 3 fractions), respectively, depending on lesion size, while sparing clinically negative brain. The treatment will be delivered using five non-coplanar arcs and a mono-isocentric technique.

Radiation: Stereotactic RadioTherapy

WBI arm

ACTIVE COMPARATOR

Patients with five or more brain metastasis assigned by randomization to Whole Brain Irradiation (WBI) will be treated using a 3D-Conformal RadioTherapy technique for a uniform dose delivery of 30 Gy in 10 daily/fractions to the target, that is entire brain.

Radiation: Whole Brain Irradiation

Interventions

Stereotactic RadioTherapy RADIATION

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).

Also known as: Stereotactic RadioSurgery, Stereotactic Body RadioTherapy

SRS/SBRT arm

Whole Brain Irradiation RADIATION

To irradiate the entire brain, site of at least 5 parenchymal metastasis.

Also known as: Whole Brain Radiotherapy, Panencephalic Radiotherapy

WBI arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mediterranean Institute of Oncology: lead
• University of Messina: collaborator
• University of Palermo: collaborator

Study Sites (4)

Fondazione Istituto Oncologico del Mediterraneo

Viagrande, Catania, 95029, Italy

RECRUITING

REM Radiotherapy (parent company of Mediterranean Institute of Oncology)

Viagrande, Catania, 95029, Italy

RECRUITING

Radiation Oncology Unit - Department of Biomedical, Dental Science and Morphological and Functional Images, University of Messina

Messina, 98125, Italy

RECRUITING

Radiation Oncology, ARNAS-Civico Hospital

Palermo, 90127, Italy

RECRUITING

Related Publications (1)

• Ferini G, Viola A, Valenti V, Tripoli A, Molino L, Marchese VA, Illari SI, Rita Borzi G, Prestifilippo A, Umana GE, Martorana E, Mortellaro G, Ferrera G, Cacciola A, Lillo S, Pontoriero A, Pergolizzi S, Parisi S. Whole Brain Irradiation or 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. Clin Transl Radiat Oncol. 2021 Dec 2;32:52-58. doi: 10.1016/j.ctro.2021.11.008. eCollection 2022 Jan.

  PMID: 34926839 DERIVED

MeSH Terms

Interventions

Radiosurgery

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Gianluca Ferini

  REM Radiotherapy (parent company of Mediterranean Institute of Oncology)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gianluca Ferini

CONTACT

+393311341117; gianluca.ferini@grupposamed.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2021
• First Posted: May 18, 2021
• Study Start: September 15, 2020
• Primary Completion: September 15, 2025
• Study Completion: September 15, 2025
• Last Updated: January 18, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

IT (4)