Clinical trial Recruiting at 1 site Interventional Ages 18 and up

MR‑Linac guided adaptive 'dose‑painting' radiation with reduced margins for Grade 4 glioma

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

Run by Sunnybrook Health Sciences Centre · NCT07459101 · Data updated 2026-11-12

This trial will test whether daily MRI‑guided adaptive 'dose‑painting' radiation with smaller treatment margins helps people with glioblastoma (Grade 4 astrocytoma) get better local tumor control and fewer side effects than standard radiation.

More Glioblastoma (GBM) trials

Quick facts

Study typeInterventional
Ages18 Years and up
SexAll
Enrollment120 (estimated)
SponsorSunnybrook Health Sciences Centre
Academic / other
Drugs / interventionsradiation, chemotherapy
Locations1 site (Toronto, Ontario)
StatusRecruiting
StartedSeptember 10, 2025
Main results expectedOctober 2029
Study endsOctober 2030
Registry record updatedOctober 23, 2026
Trial IDNCT07459101 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Ideal candidates are adults with histologically confirmed glioblastoma or WHO grade 4 astrocytoma who are appropriate for definitive concurrent chemoradiotherapy with temozolomide and had biopsy or resection within the prior 12 weeks.

Probably not a fit

Patients with contraindications to MRI, very limited expected survival, or who are not candidates for concurrent chemoradiotherapy are unlikely to benefit from this approach.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This interventional study compares an adaptive radiotherapy approach using an MR‑Linac to a standard non‑adaptive radiation approach in patients with glioblastoma or WHO grade 4 astrocytoma. Using daily MRI, clinicians will personalize radiation plans ('dose‑painting') and use reduced margins while patients receive concurrent temozolomide; treatment will be delivered either as 30 fractions over 6 weeks or 15 fractions over 3 weeks with simultaneous dose levels to high‑ and lower‑risk areas. The trial will track local control, overall and progression‑free survival, patterns of failure, toxicity, neurological function, quality of life, and longitudinal imaging features. About 60 patients are expected to be enrolled over 24 months at Sunnybrook's Odette Cancer Centre.

Why it matters

Potential benefit: If successful, this approach could maintain tumor control while lowering radiation exposure to healthy brain tissue, potentially reducing side effects and improving quality of life.

How similar studies have gone: Results from prior UNITED and UNITED‑3 studies provided supportive data, but MR‑Linac guided adaptive dose‑painting for high‑grade glioma remains under prospective validation.

Who can join: the full rules

Show full inclusion / exclusion criteria
Inclusion Criteria:

* 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)
* 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

Exclusion Criteria:

* 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)
* 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

Where it's running

  • Sunnybrook Health Sciences Centre - Odette Cancer Centre
    Toronto, Ontario, Canada
    Recruiting

Study contacts

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.