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

NCT ID: NCT04891471

Last Updated: 2023-01-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-15
• Study Completion Date: 2025-09-15

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

SRS/SBRT arm

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.

Group Type: EXPERIMENTAL

Stereotactic RadioTherapy

Intervention Type: 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).

WBI arm

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.

Group Type: ACTIVE_COMPARATOR

Whole Brain Irradiation

Intervention Type: RADIATION

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

Interventions

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).

Intervention Type: RADIATION

Whole Brain Irradiation

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

Intervention Type: RADIATION

Other Intervention Names

Stereotactic RadioSurgery; Stereotactic Body RadioTherapy; Whole Brain Radiotherapy, Panencephalic Radiotherapy

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Messina

OTHER

Sponsor Role: collaborator

University of Palermo

OTHER

Sponsor Role: collaborator

Mediterranean Institute of Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gianluca Ferini

Role: PRINCIPAL_INVESTIGATOR

REM Radiotherapy (parent company of Mediterranean Institute of Oncology)

Locations

Fondazione Istituto Oncologico del Mediterraneo

Viagrande, Catania, Italy

Site Status: RECRUITING

REM Radiotherapy (parent company of Mediterranean Institute of Oncology)

Viagrande, Catania, Italy

Site Status: RECRUITING

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

Messina, , Italy

Site Status: RECRUITING

Radiation Oncology, ARNAS-Civico Hospital

Palermo, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Gianluca Ferini

Role: CONTACT

gianluca.ferini@grupposamed.com

+393311341117

Facility Contacts

Irene R. Cravagno, Chief Radiation Oncology Unit

Role: primary

irene_rita.cravagno@fondazioneiom.it

Anna Viola, Radiation Oncologist

Role: backup

anna.viola@fondazioneiom.it

Gianluca Ferini, Chief Radiation Oncology Unit

Role: primary

gianluca.ferini@grupposamed.com

+393311341117

Silvana Parisi

Role: primary

silvana.parisi@unime.it

+393406284095

Silvana Parisi

Role: backup

silvana.parisi@unime.it

Gianluca Mortellaro

Role: primary

gianlucamortellaro@virgilio.it

3298811698

References

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.

Reference Type: DERIVED

PMID: 34926839 (View on PubMed)

Other Identifiers

70/2020/CECT2

Identifier Type: -

Identifier Source: org_study_id