Glioblastoma (GBM)UNITED-4NCT07459101
UNIty-Based MR-Linac Guided Adaptive RadioThErapy for High GraDe Glioma-4
A study testing Dose painting + Reduced Margins in people with Glioblastoma (GBM) and Astrocytoma, Grade IV, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial summary
This study builds on the results of prior studies (UNITED and UNITED-3). The goal of UNITED-4 is to test whether an adaptive radiation therapy (RT) therapy approach ('dose painting'), with reduced margins, impacts approach in participants with glioblastoma impacts local control compared to standard non-adaptive RT… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma (GBM), Astrocytoma, Grade IV
- What is being tested?
- Dose painting + Reduced Margins
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteCanada
- Study dates
- 10 Sep 2025to Oct 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Histopathologically confirmed, based on biopsy or surgical resection, glioblastoma or WHO grade 4 astrocytoma (IDH wild type or mutant)
- Deemed clinically appropriate for concurrent chemoradiotherapy (with temozolomide) with definitive/radical intent
- Biopsy or surgical resection performed ≤ 12 weeks prior to study entry
- Expected survival ≥ 12 weeks
- ECOG performance status of 0, 1 or 2
- Sufficient estimated glomerular filtration rate (eGFR) of ≥ 30 mL/ min/1.73 m2 to allow administration of gadolinium-based contrast agent; patients with eGFR < 30 mL/min/1.73 m2 not on dialysis may be allowed on the study after discussion of risks and benefits and approval by study neuroradiologist(s)
Show all 9Show fewer
- Completed written informed consent
- Patient must be accessible for treatment and follow-up
- Patients with multifocal or multicentric disease will be allowed per the discretion of the radiation oncologist
Who cannot join
- Contraindications to MRI examination as per standard MRI screening policy
- Contraindication to Gadolinium-based contrast media
- Enhancing disease involving any part of the brainstem on post-gadolinium T1-weighted MRI imaging for patients being treated using the short-course 15-fraction regimen
- Inability to lie flat in a supine position for at least 30 minutes
- Inability to tolerate immobilization in a head thermoplastic mask
- Patients > 140 kg and/or a circumference > 60 cm (MRI scanner weight and bore size limits)
Show all 10Show fewer
- Prior therapeutic cranial irradiation
- Leptomeningeal dissemination of disease
- History of other malignancies with the exception of adequately treated non-melanoma skin cancer, or curatively treated other solid tumours with no evidence of disease for ≥ 2 years
- Patients with any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Sunnybrook Health Sciences Centre - Odette Cancer Centre
Toronto, Ontario, M4N3M5
Aimee Theriault, 416-480-5000 ext. 67364, aimee.theriault@sunnybrook.ca
About this study
Official title: UNIty-Based MR-Linac Guided Adaptive RadioThErapy for High GraDe Glioma-4 (UNITED-4): Prospective Evaluation of FLAIR-Guided Clinical Target Volume Reduction
This study builds on the results of prior studies (UNITED and UNITED-3). The goal of UNITED-4 is to test whether an adaptive radiation therapy (RT) therapy approach ('dose painting'), with reduced margins, impacts approach in participants with glioblastoma impacts local control compared to standard non-adaptive RT approach. The main questions of the study are to see how this adaptive RT approach with reduced margins compares to standard RT in terms of:
- Local control
- Overall and progression-free survival
- Patterns of failure
- Toxicity, Neurological Function, and Quality of Life
- Longitudinal imaging features
Read the detailed description
The UNITED-4 study is for people diagnosed with glioblastoma (GBM) or other high-grade (aggressive) brain tumors. These tumors are typically treated with radiation therapy combined with a chemotherapy agent called temozolomide. Standard radiation for these tumours uses a wide margin around the tumor to ensure that all areas potentially at risk for the presence of cancer cells are targeted, but this approach can also damage healthy brain tissue.
The UNITED-4 trial uses a new machine called an MR-Linac, which combines a radiation machine with an magnetic resonance imaging (MRI) scanner, allowing doctors to take daily images during treatment and adjust the radiation plan in real-time. This study will personalize treatment based on fluid-attenuated inversion recovery (FLAIR) MRI imaging that shows where cancer cells might be spreading while using smaller treatment margins to protect more of the normal brain. Patients will receive either 30 treatments over 6 weeks or 15 treatments over 3 weeks, with different radiation doses delivered simultaneously to high-risk areas (tumour) and lower-risk areas (normal brain). The goal of this study is to determine if this approach maintains cancer control while potentially reducing side effects and improving quality of life compared to standard treatments. Risks include radiation side effects (expected to be no worse than standard treatment) and a possibility of tumor recurrence at treatment edges.
The study will enroll 60 patients over 24 months at Sunnybrook Health Sciences Centre.
- Conditions
- Glioblastoma (GBM), Astrocytoma, Grade IV
- Being tested
- Dose painting + Reduced Margins
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dose painting + Reduced MarginsRadiation
Reduced margins using a dose painting approach
| Study group | Role | What they receive |
|---|---|---|
| Adaptive RT (Dose Painting) | Experimental | Participants in this arm will have radiation (with reduced margins) delivered using a dose painting approach Receives: Radiation: Dose painting + Reduced Margins |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease worsening at 6 months
Measured: From RT start to 6 months after RT
Secondary outcomes (7)
Overall survival
Measured: Throughout study participation, anticipated 0-25 months
Type of progression
Whether the progression occurred at local, marginal, or distant location
Measured: Throughout study participation, anticipated 0-25 months
Number of participants with RT-related adverse events as assessed by CTCAE v5.0
Acute (within 3 months of RT completion) and late (> 3 months of RT completion) effects will be assessed
Measured: Throughout study participation, anticipated 0-25 months
Neurological Function
Will be assessed by your treating doctor, using the Neurological Assessment in Neuro-Oncology (NANO) scale
Measured: Throughout study participation, anticipated 0-25 months
Imaging features as correlates of treatment outcomes
Measured: Throughout study participation, anticipated 0-25 months
Changes in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
This is one of the questionnaires that will be used to qualitatively assess the changes to your quality of life (neurological function, symptoms, and overall status), during your participation on the study. A higher scale score represents a higher response level with regards to the measured item.
Measured: Throughout study participation, anticipated 0-25 months
Changes in the European Organisation for Research and Treatment of Cancer Brain Cancer Module (EORTC QLQ-BN20)
This questionnaire is used together with QLQ-C30 to qualitatively assess changes in your symptoms during your participation on the study. A higher scale score represents more, or more severe, symptoms.
Measured: Throughout study participation, anticipated 0-25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2026
- Study start10 Sep 2025
- Primary completionOct 2029 (estimated)
- Study completionOct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma (GBM)Studies of the same condition, open and under way.
- 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
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07459101
- Sponsor's protocol ID
- UNITED-4
- Acronym
- UNITED-4
- Status last verified
- Oct 2025
- First submitted
- 17 Nov 2025
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2026. 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-4 (UNITED-4): Prospective Evaluation of FLAIR-Guided Clinical Target Volume Reduction
- ClinicalTrials.gov ID
- NCT07459101
- Acronym / sponsor ID
- UNITED-4 / UNITED-4
- Conditions
- Glioblastoma (GBM), Astrocytoma, Grade IV
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 10 Sep 2025 (actual)
- Primary completion
- Oct 2029 (estimated)
- Study completion
- Oct 2030 (estimated)
- First posted
- 9 Mar 2026 (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.
This study builds on the results of prior studies (UNITED and UNITED-3). The goal of UNITED-4 is to test whether an adaptive radiation therapy (RT) therapy approach ('dose painting'), with reduced margins, impacts approach in participants with glioblastoma impacts local control compared to standard non-adaptive RT approach. The main questions of the study are to see how this adaptive RT approach with reduced margins compares to standard RT in terms of:
- Local control
- Overall and progression-free survival
- Patterns of failure
- Toxicity, Neurological Function, and Quality of Life
- Longitudinal imaging features
Detailed description
The UNITED-4 study is for people diagnosed with glioblastoma (GBM) or other high-grade (aggressive) brain tumors. These tumors are typically treated with radiation therapy combined with a chemotherapy agent called temozolomide. Standard radiation for these tumours uses a wide margin around the tumor to ensure that all areas potentially at risk for the presence of cancer cells are targeted, but this approach can also damage healthy brain tissue.
The UNITED-4 trial uses a new machine called an MR-Linac, which combines a radiation machine with an magnetic resonance imaging (MRI) scanner, allowing doctors to take daily images during treatment and adjust the radiation plan in real-time. This study will personalize treatment based on fluid-attenuated inversion recovery (FLAIR) MRI imaging that shows where cancer cells might be spreading while using smaller treatment margins to protect more of the normal brain. Patients will receive either 30 treatments over 6 weeks or 15 treatments over 3 weeks, with different radiation doses delivered simultaneously to high-risk areas (tumour) and lower-risk areas (normal brain). The goal of this study is to determine if this approach maintains cancer control while potentially reducing side effects and improving quality of life compared to standard treatments. Risks include radiation side effects (expected to be no worse than standard treatment) and a possibility of tumor recurrence at treatment edges.
The study will enroll 60 patients over 24 months at Sunnybrook Health Sciences Centre.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adaptive RT (Dose Painting) | Experimental | Radiation: Dose painting + Reduced MarginsParticipants in this arm will have radiation (with reduced margins) delivered using a dose painting approach |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histopathologically confirmed, based on biopsy or surgical resection, glioblastoma or WHO grade 4 astrocytoma (IDH wild type or mutant)
- Deemed clinically appropriate for concurrent chemoradiotherapy (with temozolomide) with definitive/radical intent
- Biopsy or surgical resection performed ≤ 12 weeks prior to study entry
- Expected survival ≥ 12 weeks
- ECOG performance status of 0, 1 or 2
Key exclusion criteria (10 listed)
- Contraindications to MRI examination as per standard MRI screening policy
- Contraindication to Gadolinium-based contrast media
- Enhancing disease involving any part of the brainstem on post-gadolinium T1-weighted MRI imaging for patients being treated using the short-course 15-fraction regimen
- Inability to lie flat in a supine position for at least 30 minutes
- Inability 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 |
|---|---|---|
| Dose painting + Reduced MarginsReduced margins using a dose painting approach | Radiation | Adaptive RT (Dose Painting) |
Primary outcome
Disease worsening at 6 months
Time frame: From RT start to 6 months after RT
7 secondary outcomes
Overall survival
Time frame: Throughout study participation, anticipated 0-25 months
Type of progression
Time frame: Throughout study participation, anticipated 0-25 months
Number of participants with RT-related adverse events as assessed by CTCAE v5.0
Time frame: Throughout study participation, anticipated 0-25 months
Neurological Function
Time frame: Throughout study participation, anticipated 0-25 months
Imaging features as correlates of treatment outcomes
Time frame: Throughout study participation, anticipated 0-25 months
Changes in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
Time frame: Throughout study participation, anticipated 0-25 months
Changes in the European Organisation for Research and Treatment of Cancer Brain Cancer Module (EORTC QLQ-BN20)
Time frame: Throughout study participation, anticipated 0-25 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Glioblastoma (GBM)
Not yet recruiting
A Single-Arm, Open-Label, Multicenter Clinical Study of Teniposide Combined With Temozolomide for the Treatment of Newly Diagnosed Glioblastoma (nGBM) With MGMT Promotor Region Unmethylated
Newly Diagnosed Glioblastoma, MGMT-Unmethylated Glioblastoma
Active, not recruitingPhase 1/2
Ultrasound-based Blood-brain Barrier Opening and Albumin-bound Paclitaxel and Carboplatin for Recurrent Glioblastoma
Glioblastoma, Gliosarcoma
RecruitingPhase 2
Temozolomide, With or Without WSD0922-FU, for the Treatment of EGFR-Mutant, IDH-Wildtype Glioblastoma
Glioblastoma, IDH-Wildtype
Active, not recruitingPhase 1
Safety and Efficacy Study of Anti-B7-H3 CAR-T Cell Therapy for Recurrent Glioblastoma
Glioblastoma
Active, not recruitingPhase 2
A Study Testing the Effect of Immunotherapy (Ipilimumab and Nivolumab) in Patients With Recurrent Glioma With Elevated Mutational Burden
Astrocytoma, IDH-Mutant, Grade 4, Diffuse Glioma
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dose painting + Reduced Margins in people with Glioblastoma (GBM) and Astrocytoma, Grade IV, 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 9 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 23 Oct 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hanbo Chen, MD (416-480-6100, hanbo.chen@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease worsening at 6 months (time frame: From RT start to 6 months after RT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Oct 2026.