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Active, Not Recruiting

NCT Number: NCT05565521

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Glioblastoma Multiforme, Adult Astrocytoma Glioblastoma Glioblastoma, IDH-mutant Glioma Neoplasms Neoplasms by Histologic Type Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neuroectodermal Tumors

Age range

65 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Odette Cancer Centre, Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

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.

Primary outcomes

  1. Progression-free survival at 6 months following chemoradiation

    Time frame: 6 months from study entry date

Secondary outcomes

  1. Overall survival

    Time frame: Through study completion, an average of 9 months

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

  2. Progression-free survival

    Time frame: Through study completion, an average of 5 months

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

  3. Local control

    Time frame: Through study completion, an average of 5 months

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

  4. Patterns of Failure

    Time frame: Through study completion, an average of 5 months

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

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

    Time frame: Through study completion, an average of 9 months

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

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

    Time frame: Through study completion, an average of 9 months

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

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

    Time frame: 6-12 months

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

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

    Time frame: 6-12 months

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

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

    Time frame: 6-12 months

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

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

    Time frame: 6-12 months

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

  11. Functional Imaging Kinetics as a Correlate of Treatment Response

    Time frame: 12-24 months

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

Sponsors and collaborators

Lead sponsor

Sunnybrook Health Sciences Centre

Other

Registry information

Acronym: UNITED2

Important dates

Study start
2022
Primary completion
2027
Study completion
2028
First posted
Oct 4, 2022
Registry last updated
Apr 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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