Glioblastoma MultiformeUNITEDNCT04726397
UNIty-Based MR-Linac Guided AdapTive RadiothErapy for High GraDe Glioma: a Phase 2 Trial
A study testing Reduced margin adaptive radiotherapy in people with Glioblastoma Multiforme, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial summary
Glioblastoma (GBM) is a high grade glioma (brain tumor) that is treated with surgery or biopsy followed by radiotherapy (RT) given daily over 3 or 6 weeks with or without an oral chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Reduced margin adaptive radiotherapy
- Type of treatment
- Surgery or procedure
- How many people
- 108 participants
- Where
- 1 siteCanada
- Study dates
- 29 Mar 2021to 15 May 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 18 years and older
- Histopathologically confirmed malignant glioma of the brain, Grade 4 (GBM)
- Eligible for RT in 15 or 30 fractions with or without chemotherapy (temozolamide)
- Expected survival greater than 12 weeks
- WHO performance status less than or equal to 2
- Able to converse and answer questionnaires in English language
- Has a maximum final planning volume less than 150 cm3
Who cannot join
- Contraindications to MRI examination as per standard MRI screening policy
- Contraindication to Gadolinium-based contrast media
- Unable to lie flat in a supine position for 30 minutes
- Poor baseline kidney function with an eGFR < 60 mL/min
- Unable to tolerate immobilization in a head thermoplastic mask
- Patients >140 kg and/or a circumference >60cm
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- Previous cranial irradiation
- Infratentorial tumour extent, multifocal of leptomeningeal disease
- Unable to give informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: UNIty-Based MR-Linac Guided AdapTive RadiothErapy for High GraDe Glioma: a Phase 2 Trial (UNITED Trial)
Glioblastoma (GBM) is a high grade glioma (brain tumor) that is treated with surgery or biopsy followed by radiotherapy (RT) given daily over 3 or 6 weeks with or without an oral chemotherapy. Radiation is targeted to the visible residual tumor on magnetic resonance imaging (MRI) images plus a large margin of 15 to 30 mm to account for possible cancer cells outside the visible tumor and for potential growth or shifts in tumor position throughout the prolonged RT course. Standard RT uses MRI to create a reference plan (with large margins) and treats that same volume every day. This exposes a large amount of healthy brain tissue to radiation leading to toxicity and reduced quality of life.
A new technology, the MR-Linac, combines an MRI scanner and a Linac (radiation delivery machine) into one unit. This allows for "adaptive" RT by obtaining an updated MRI scan each day just prior to treatment, adapting the RT plan to take into account any changes in the tumor or the patient's anatomy on that given day. This allows for a smaller (5 mm) margin on the visible tumor as its position can be tracked daily. The goal of this study is to use adaptive RT with small margins to demonstrate that the local control of the visible tumor is not compromised compared to the large volumes used with standard non-adaptive RT, while determining whether smaller margins lead to decreased radiation toxicity and therefore improved quality of life by minimizing radiation exposure.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Reduced margin adaptive radiotherapy
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reduced margin adaptive radiotherapyRadiation
Reduced (5 mm) clinical target volume margin with weekly contrast-enhanced adaptive radiation on the MR-Linac treatment machine
What is being measured
The primary outcome is the main question the study is designed to answer.
Imaging-detected tumor recurrence at the edge of the radiation volume ("marginal" failure)
The presence of tumor on contrast-enhanced MRI between 1-2 cm from the edge of the treated radiation volume (commonly known as a marginal failure) within 1 year from radiation.
Measured: Within 1 year from end of radiation
Secondary outcomes (5)
Tumor volume changes during RT
Change in gross tumor volume (%) from start to end of RT
Measured: 6 weeks
Acute radiation toxicity based on RTOG/EORTC Common Toxicity Criteria
Grades 1-4 toxicity during RT in the following categories: skin, CNS, eye, ear, and hematological
Measured: 6 weeks
Quality of life changes based on EORTC QLQ-C30
Changes in quality of life during and after RT based on accepted EORTC cancer quality of life instruments administered each week on RT, 1 month post RT, and every 3 months subsequently
Measured: 1 year
Dexamethasone usage
Amount of dexamethasone required during RT
Measured: 10 weeks
Quality of life based on EORTC QLQ-BN20
Changes in quality of life during and after RT based on accepted EORTC brain tumor quality of life instruments administered each week on RT, 1 month post RT, and every 3 months subsequently
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2021
- Study start29 Mar 2021
- Primary completion15 May 2024
- Study completion15 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jay Detsky, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04726397
- Sponsor's protocol ID
- 3412
- Acronym
- UNITED
- Status last verified
- Nov 2024
- First submitted
- 19 Jan 2021
- Last updated
- 29 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Detsky JS, Chan AW, Moore-Palhares D, Safavi AH, Perry J, Fat MJL, Atenafu EG, Das S, Lipsman N, Heyn C, Maralani P, Czarnota GJ, Ruschin M, Keller B, Lau A, Chen H, Myrehaug SD, Soliman H, Tseng CL, Sahgal A. MRI-guided adaptive radiotherapy for high grade glioma (UNITED): a single-centre, single-arm, non-inferiority, phase 2 trial. Lancet Oncol. 2026 Jun;27(6):729-737. doi: 10.1016/S1470-2045(26)00088-4. Epub 2026 May 14.
PubMed 42134380Lawrence LSP, Chan RW, Chen H, Stewart J, Ruschin M, Theriault A, Myrehaug S, Detsky J, Maralani PJ, Tseng CL, Soliman H, Jane Lim-Fat M, Das S, Stanisz GJ, Sahgal A, Lau AZ. Diffusion-weighted imaging on an MRI-linear accelerator to identify adversely prognostic tumour regions in glioblastoma during chemoradiation. Radiother Oncol. 2023 Nov;188:109873. doi: 10.1016/j.radonc.2023.109873. Epub 2023 Aug 26.
PubMed 37640160
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- UNIty-Based MR-Linac Guided AdapTive RadiothErapy for High GraDe Glioma: a Phase 2 Trial (UNITED Trial)
- ClinicalTrials.gov ID
- NCT04726397
- Acronym / sponsor ID
- UNITED / 3412
- Conditions
- Glioblastoma Multiforme
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 29 Mar 2021 (actual)
- Primary completion
- 15 May 2024 (actual)
- Study completion
- 15 May 2024 (actual)
- First posted
- 27 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Glioblastoma (GBM) is a high grade glioma (brain tumor) that is treated with surgery or biopsy followed by radiotherapy (RT) given daily over 3 or 6 weeks with or without an oral chemotherapy. Radiation is targeted to the visible residual tumor on magnetic resonance imaging (MRI) images plus a large margin of 15 to 30 mm to account for possible cancer cells outside the visible tumor and for potential growth or shifts in tumor position throughout the prolonged RT course. Standard RT uses MRI to create a reference plan (with large margins) and treats that same volume every day. This exposes a large amount of healthy brain tissue to radiation leading to toxicity and reduced quality of life.
A new technology, the MR-Linac, combines an MRI scanner and a Linac (radiation delivery machine) into one unit. This allows for "adaptive" RT by obtaining an updated MRI scan each day just prior to treatment, adapting the RT plan to take into account any changes in the tumor or the patient's anatomy on that given day. This allows for a smaller (5 mm) margin on the visible tumor as its position can be tracked daily. The goal of this study is to use adaptive RT with small margins to demonstrate that the local control of the visible tumor is not compromised compared to the large volumes used with standard non-adaptive RT, while determining whether smaller margins lead to decreased radiation toxicity and therefore improved quality of life by minimizing radiation exposure.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients aged 18 years and older
- Histopathologically confirmed malignant glioma of the brain, Grade 4 (GBM)
- Eligible for RT in 15 or 30 fractions with or without chemotherapy (temozolamide)
- Expected survival greater than 12 weeks
- WHO performance status less than or equal to 2
Key exclusion criteria (9 listed)
- Contraindications to MRI examination as per standard MRI screening policy
- Contraindication to Gadolinium-based contrast media
- Unable to lie flat in a supine position for 30 minutes
- Poor baseline kidney function with an eGFR < 60 mL/min
- Unable to tolerate immobilization in a head thermoplastic mask
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Reduced margin adaptive radiotherapyReduced (5 mm) clinical target volume margin with weekly contrast-enhanced adaptive radiation on the MR-Linac treatment machine | Radiation | – |
Primary outcome
Imaging-detected tumor recurrence at the edge of the radiation volume ("marginal" failure)
Time frame: Within 1 year from end of radiation
The presence of tumor on contrast-enhanced MRI between 1-2 cm from the edge of the treated radiation volume (commonly known as a marginal failure) within 1 year from radiation.
5 secondary outcomes
Tumor volume changes during RT
Time frame: 6 weeks
Acute radiation toxicity based on RTOG/EORTC Common Toxicity Criteria
Time frame: 6 weeks
Quality of life changes based on EORTC QLQ-C30
Time frame: 1 year
Dexamethasone usage
Time frame: 10 weeks
Quality of life based on EORTC QLQ-BN20
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2024.
- Derived from this study: PubMed 42134380Detsky JS, Chan AW, Moore-Palhares D, Safavi AH, Perry J, Fat MJL, Atenafu EG, Das S, Lipsman N, Heyn C, Maralani P, Czarnota GJ, Ruschin M, Keller B, Lau A, Chen H, Myrehaug SD, Soliman H, Tseng CL, Sahgal A. MRI-guided adaptive radiotherapy for high grade glioma (UNITED): a single-centre, single-arm, non-inferiority, phase 2 trial. Lancet Oncol. 2026 Jun;27(6):729-737. doi: 10.1016/S1470-2045(26)00088-4. Epub 2026 May 14.
- Derived from this study: PubMed 37640160Lawrence LSP, Chan RW, Chen H, Stewart J, Ruschin M, Theriault A, Myrehaug S, Detsky J, Maralani PJ, Tseng CL, Soliman H, Jane Lim-Fat M, Das S, Stanisz GJ, Sahgal A, Lau AZ. Diffusion-weighted imaging on an MRI-linear accelerator to identify adversely prognostic tumour regions in glioblastoma during chemoradiation. Radiother Oncol. 2023 Nov;188:109873. doi: 10.1016/j.radonc.2023.109873. Epub 2023 Aug 26.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Reduced margin adaptive radiotherapy in people with Glioblastoma Multiforme, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Imaging-detected tumor recurrence at the edge of the radiation volume ("marginal" failure) (time frame: Within 1 year from end of radiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04726397, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2024.