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

January 16, 2023 updated by: Mediterranean Institute of Oncology

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Messina, Italy, 98125
        • Recruiting
        • Radiation Oncology Unit - Department of Biomedical, Dental Science and Morphological and Functional Images, University of Messina
        • Contact:
        • Contact:
        • Principal Investigator:
          • Silvana Parisi
        • Principal Investigator:
          • Stefano Pergolizzi
        • Sub-Investigator:
          • Antonio Pontoriero
        • Principal Investigator:
          • Alberto Cacciola
        • Sub-Investigator:
          • Sara Lillo
      • Palermo, Italy, 90127
        • Recruiting
        • Radiation Oncology, ARNAS-Civico Hospital
        • Contact:
        • Sub-Investigator:
          • Giuseppe Ferrera
    • Catania
      • Viagrande, Catania, Italy, 95029
      • Viagrande, Catania, Italy, 95029
        • Recruiting
        • REM Radiotherapy (parent company of Mediterranean Institute of Oncology)
        • Contact:
        • Principal Investigator:
          • Gianluca Ferini
        • Sub-Investigator:
          • Vito Valenti
        • Sub-Investigator:
          • Antonella Tripoli

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
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).
Other Names:
  • Stereotactic RadioSurgery
  • Stereotactic Body RadioTherapy
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.
Radiation: Whole Brain Irradiation
To irradiate the entire brain, site of at least 5 parenchymal metastasis.
Other Names:
  • Whole Brain Radiotherapy, Panencephalic Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurocognitive changes detected through Moca Score
Time Frame: Change from Baseline pre-Radiotherapy Neurocognitive Functional Status every three months after treatment through study completion, an average of 1 year
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
Time Frame: Change from Baseline pre-Radiotherapy Barthel Index every three months after treatment through study completion, an average of 1 year
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
Time Frame: Change from Baseline pre-Radiotherapy EORTC QLQ-C15-PAL questionnaire every three months after treatment through study completion, an average of 1 year
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
Time Frame: Change from Baseline pre-Radiotherapy Neurocognitive Functional Status every three months after treatment through study completion, an average of 1 year
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
Time Frame: Change from Baseline pre-Radiotherapy BN-20 questionnaire every three months after treatment through study completion, an average of 1 year
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to local failure
Time Frame: every three months after treatment through study completion, an average of 1 year
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
Overall Survival
Time Frame: after treatment completion through study completion, an average of 1 year
Time from the first day of treatment to exitus
after treatment completion through study completion, an average of 1 year
Re-treatment rate
Time Frame: after first treatment completion through study completion, an average of 1 year
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
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
Time Frame: from treatment completion until three months later
Toxicities registered within three months from treatment
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
Time Frame: from three months after treatment completion through study completion, an average of 1 year
Toxicities registered after three months from treatment
from three months after treatment completion through study completion, an average of 1 year
Karnofsky Performance Status changing
Time Frame: after treatment completion through study completion, an average of 1 year
Evaluation of how patient's performance status modifies after treatment
after treatment completion through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mediterranean Institute of Oncology

Collaborators

University of Palermo
University of Messina

Investigators

  • Principal Investigator: Gianluca Ferini, REM Radiotherapy (parent company of Mediterranean Institute of Oncology)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 15, 2020

Primary Completion (Anticipated)

September 15, 2025

Study Completion (Anticipated)

September 15, 2025

Study Registration Dates

First Submitted

April 20, 2021

First Submitted That Met QC Criteria

May 13, 2021

First Posted (Actual)

May 18, 2021

Study Record Updates

Last Update Posted (Actual)

January 18, 2023

Last Update Submitted That Met QC Criteria

January 16, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 70/2020/CECT2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Sharing Supporting Information Type

  • Study Protocol

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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