Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04891471
Recruitment Status : Recruiting
First Posted : May 18, 2021
Last Update Posted : May 18, 2021
Sponsor:
Collaborators:
University of Messina
University of Palermo
Information provided by (Responsible Party):
Mediterranean Institute of Oncology

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.

Condition or disease Intervention/treatment Phase
Neurocognitive Deficit Quality of Life Activities of Daily Living Radiation: Stereotactic RadioTherapy Radiation: Whole Brain Irradiation Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Actual Study Start Date : September 15, 2020
Estimated Primary Completion Date : September 15, 2025
Estimated Study Completion Date : September 15, 2025

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 Name: Whole Brain Radiotherapy, Panencephalic Radiotherapy




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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


Secondary Outcome Measures :
  1. 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

  2. Overall Survival [ Time Frame: after treatment completion through study completion, an average of 1 year ]
    Time from the first day of treatment to exitus

  3. 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

  4. 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

  5. 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

  6. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04891471


Contacts
Layout table for location contacts
Contact: Gianluca Ferini +393311341117 gianluca.ferini@grupposamed.com

Locations
Layout table for location information
Italy
Fondazione Istituto Oncologico del Mediterraneo Recruiting
Viagrande, Catania, Italy, 95029
Contact: Irene R. Cravagno, Chief Radiation Oncology Unit       irene_rita.cravagno@fondazioneiom.it   
Contact: Anna Viola, Radiation Oncologist       anna.viola@fondazioneiom.it   
Principal Investigator: Anna Viola, Radiation Oncologist         
REM Radiotherapy (parent company of Mediterranean Institute of Oncology) Recruiting
Viagrande, Catania, Italy, 95029
Contact: Gianluca Ferini, Chief Radiation Oncology Unit    +393311341117    gianluca.ferini@grupposamed.com   
Principal Investigator: Gianluca Ferini         
Sub-Investigator: Vito Valenti         
Sub-Investigator: Antonella Tripoli         
Radiation Oncology Unit - Department of Biomedical, Dental Science and Morphological and Functional Images, University of Messina Recruiting
Messina, Italy, 98125
Contact: Silvana Parisi    +393406284095    silvana.parisi@unime.it   
Contact: Silvana Parisi       silvana.parisi@unime.it   
Principal Investigator: Silvana Parisi         
Principal Investigator: Stefano Pergolizzi         
Sub-Investigator: Antonio Pontoriero         
Principal Investigator: Alberto Cacciola         
Sub-Investigator: Sara Lillo         
Radiation Oncology, ARNAS-Civico Hospital Recruiting
Palermo, Italy, 90127
Contact: Gianluca Mortellaro    3298811698    gianlucamortellaro@virgilio.it   
Sub-Investigator: Giuseppe Ferrera         
Sponsors and Collaborators
Mediterranean Institute of Oncology
University of Messina
University of Palermo
Investigators
Layout table for investigator information
Principal Investigator: Gianluca Ferini REM Radiotherapy (parent company of Mediterranean Institute of Oncology)
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Mediterranean Institute of Oncology
ClinicalTrials.gov Identifier: NCT04891471    
Other Study ID Numbers: 70/2020/CECT2
First Posted: May 18, 2021    Key Record Dates
Last Update Posted: May 18, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mediterranean Institute of Oncology:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases