UNIty-Based MR-Linac Guided Adaptive RadioThErapy for High GraDe Glioma-4

NCT07459101 | Recruiting

• 1 other identifier: UNITED-4
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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 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

Conditions

Glioblastoma (GBM); Astrocytoma, Grade IV

Outcome Measures

Primary Outcomes (1)

• Disease worsening at 6 months

  From RT start to 6 months after RT

Secondary Outcomes (7)

• Overall survival

  Throughout study participation, anticipated 0-25 months

• Type of progression

  Throughout study participation, anticipated 0-25 months

• Number of participants with RT-related adverse events as assessed by CTCAE v5.0

  Throughout study participation, anticipated 0-25 months

• Neurological Function

  Throughout study participation, anticipated 0-25 months

• Imaging features as correlates of treatment outcomes

  Throughout study participation, anticipated 0-25 months

Study Arms (1)

Adaptive RT (Dose Painting)

EXPERIMENTAL

Participants in this arm will have radiation (with reduced margins) delivered using a dose painting approach

Radiation: Dose painting + Reduced Margins

Interventions

Dose painting + Reduced Margins RADIATION

Reduced margins using a dose painting approach

Adaptive RT (Dose Painting)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre - Odette Cancer Centre

Toronto, Ontario, M4N3M5, Canada

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Central Study Contacts

Hanbo Chen, MD

CONTACT

416-480-6100; hanbo.chen@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: March 9, 2026
• Study Start: September 10, 2025
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2030
• Last Updated: March 9, 2026

Record last verified: 2025-10

Locations

CA (1)