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

Phase 2RecruitingNCT05565521

Sunnybrook Health Sciences Centre55 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Glioblastoma Multiforme, Adult Glioblastoma, IDH-mutant

Eligibility

Sex: ALLMin age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Progression-free survival at 6 months following chemoradiation

Time frame: 6 months from study entry date

Secondary Outcomes

Overall survival

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

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

Progression-free survival

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

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

Local control

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

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

Patterns of Failure

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

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

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

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

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

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

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

Time frame: 6-12 months

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

Time frame: 6-12 months

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

Time frame: 6-12 months

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

Time frame: 6-12 months

Functional Imaging Kinetics as a Correlate of Treatment Response

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

Time frame: 12-24 months

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts