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Glioblastoma Multiforme, AdultPhase 2UNITED2NCT05565521

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

A Phase 2 study testing Dose escalation + Reduced Margin Adaptive Radiotherapy in people with Glioblastoma Multiforme, Adult and Glioblastoma, IDH-mutant, run by Sunnybrook Health Sciences Centre at 1 site in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 65 years and older
What is being tested?
Dose escalation + Reduced Margin Adaptive Radiotherapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
1 siteCanada
Study dates
13 Dec 2022to 31 Dec 2028
Phase
Phase 2
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 65 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Odette Cancer Centre, Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

Other trials in Canada

About this study

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.

Being tested
Dose escalation + 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.

  • Dose escalation + Reduced Margin Adaptive RadiotherapyRadiation

    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.

Study groups in NCT05565521
Study groupRoleWhat they receive
Treatment ArmExperimentalConcurrent dose-escalated chemoradiation with temozolomide (TMZ) on the MR-Linac with weekly adaptation
Receives: Radiation: Dose escalation + Reduced Margin Adaptive Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival at 6 months following chemoradiation

    Measured: 6 months from study entry date

Secondary outcomes (11)

  1. Overall survival

    The time interval between study start date and date of death from any cause

    Measured: Through study completion, an average of 9 months

  2. Progression-free survival

    The time interval between study start date and date of disease progression or death, whichever comes first

    Measured: Through study completion, an average of 5 months

  3. Local control

    As assessed on imaging using the Response Assessment Criteria for High-Grade Gliomas (RANO-HGG)

    Measured: Through study completion, an average of 5 months

  4. Patterns of Failure

    The risk of local, marginal, and distant failure at the time of progression

    Measured: Through study completion, an average of 5 months

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

    Adverse events and changes in quality of life before, during, and after chemoradiation therapy

    Measured: Through study completion, an average of 9 months

  6. Toxicity and Health-related Quality of Life Changes based on the EORTC QLQ-BN20

    Adverse events and changes in quality of life before, during, and after chemoradiation therapy

    Measured: Through study completion, an average of 9 months

  7. Compare differences in adaptive vs non-adaptive with regards to treatment volume

    Differences in treatment volume using adaptive vs. non-adaptive treatment planning will be compared

    Measured: 6-12 months

  8. Compare differences in adaptive vs non-adaptive with regards to organ-at-risk doses

    Differences in dosing to organs-at-risk using adaptive vs. non-adaptive treatment planning will be compared

    Measured: 6-12 months

  9. Compare differences in adaptive vs non-adaptive with regards to cumulative dose

    Differences in cumulative dose of radiation using adaptive vs. non-adaptive treatment planning will be compared

    Measured: 6-12 months

  10. Compare differences in adaptive vs non-adaptive with regards to length of radiation treatment time

    Differences in time for radiation treatment using adaptive vs. non-adaptive treatment planning will be compared

    Measured: 6-12 months

  11. Functional Imaging Kinetics as a Correlate of Treatment Response

    Temporal changes of functional imaging metrics will be correlated with clinical outcomes

    Measured: 12-24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Oct 2022
  2. Study start13 Dec 2022
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
55 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05565521
Sponsor's protocol ID
UNITED2
Acronym
UNITED2
Status last verified
Apr 2026
First submitted
23 Sep 2022
Last updated
24 Apr 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dose escalation + Reduced Margin Adaptive Radiotherapy in people with Glioblastoma Multiforme, Adult and Glioblastoma, IDH-mutant, 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 10 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: under way, not looking for participants, as of the sponsor's last update on 24 Apr 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

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?

Progression-free survival at 6 months following chemoradiation (time frame: 6 months from study entry date). 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 NCT05565521.

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 24 Apr 2026; AzTrials last refreshed its copy on 27 Oct 2026.

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