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

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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	65 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05565521
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Sunnybrook Health Sciences Centre
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Canada
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Glioblastoma Multiforme, Adult, Glioblastoma, IDH-mutant

Arms & Interventions

Arms

Experimental: Treatment Arm

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

Interventions

Radiation: - Dose escalation + Reduced Margin Adaptive Radiotherapy

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.