UNITy-BasED MR-Linac Adaptive Simultaneous Integrated Hypofractionated Boost Trial for High Grade Glioma in the Elderly

NCT05565521 | Active Not Recruiting Phase 2

• 1 other identifier: UNITED2
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

The usual standard of care for patients over 65 diagnosed with glioblastoma ("GBM") or Grade 4 astrocytoma, IDH-mutant is a 3-week course of radiotherapy, with concurrent and adjuvant temozolomide (TMZ). This radiation dose and length of treatment are less than what would be given for younger patients, primarily due to unclear survival benefits from randomized trials. However, survival remains dismal, and may be partially due to the reduced radiation dose. Recent studies investigating this have found that increased radiation dose (to the equivalent of what is normally given over 6 weeks in younger patients) over 3 weeks is well-tolerated and has improved survival rates. Additionally, with the advent of novel technology such as the MR-Linac, adaptive radiotherapy with this regimen using reduced radiation margins is possible. Use of the MR-Linac allows for daily MRI scans to be done prior to treatment, so plans can be adapted to tumour dynamics and anatomical deformations. In this trial, we will examine the outcomes of increased radiation dose, combined with reduced-margin adaptive radiotherapy in this patient population.

Conditions

Glioblastoma Multiforme, Adult; Glioblastoma, IDH-mutant

Outcome Measures

Primary Outcomes (1)

• Progression-free survival at 6 months following chemoradiation

  6 months from study entry date

Secondary Outcomes (11)

• Overall survival

  Through study completion, an average of 9 months

• Progression-free survival

  Through study completion, an average of 5 months

• Local control

  Through study completion, an average of 5 months

• Patterns of Failure

  Through study completion, an average of 5 months

• Toxicity and Health-related Quality of Life Changes based on the EORTC QLQ-C30

  Through study completion, an average of 9 months

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Concurrent dose-escalated chemoradiation with temozolomide (TMZ) on the MR-Linac with weekly adaptation

Radiation: Dose escalation + Reduced Margin Adaptive Radiotherapy

Interventions

Dose escalation + Reduced Margin Adaptive Radiotherapy RADIATION

Concurrent chemoradiation with temozolomide (TMZ) over 3 weeks (40 Gy in 15 fractions). The gross tumor volume (GTV) plus margin will be boosted simultaneously (SIB) to 52.5 Gy in 15 fractions. Radiation will be delivered on the MR-Linac with a reduced clinical target volume (CTV) margin of minimum 5 mm and a weekly online adaptive approach.

Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Patient age ≥ 65 years
• Histopathologically confirmed, based on biopsy or surgical resection, glioblastoma or WHO grade 4 astrocytoma, IDH-mutant
• Biopsy or surgical resection performed ≤ 6 weeks prior to study entry
• Deemed suitable by the treating physicians for 15 daily fractions of radiation, delivered daily over 3 weeks, with concurrent temozolomide chemotherapy
• Expected survival ≥ 12 weeks
• ECOG performance status of 0, 1 or 2
• Able (sufficiently fluent in English) and willing to complete QOL questionnaires; however, inability to complete the questionnaires will not make the patient ineligible for the study
• 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

You may not qualify if:

• Contraindications to MRI as per standard MRI screening policy
• Contraindication to Gadolinium-based contrast media
• Inability to lie flat in a supine position for at least 90 minutes
• Inability to tolerate immobilization in a head thermoplastic mask
• Patients \> 140 kg and/or a circumference \> 60 cm
• Prior dose-limiting cranial irradiation
• T1w post-gadolinium enhancing disease involving the brainstem
• Leptomeningeal dissemination of disease
• 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)

Odette Cancer Centre, Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Radiation Oncology

Study Record Dates

• First Submitted: September 23, 2022
• First Posted: October 4, 2022
• Study Start: December 13, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)