Clinical trial NCT04726397: UNIty-Based MR-Linac Guided AdapTive RadiothErapy for High GraDe Glioma: a Phase 2 Trial
Official title: UNIty-Based MR-Linac Guided AdapTive RadiothErapy for High GraDe Glioma: a Phase 2 Trial (UNITED Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glioblastoma Multiforme
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
First posted: 2021-01-27
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Glioblastoma (GBM) is a high grade glioma (brain tumor) that is treated with surgery or biopsy followed by radiotherapy (RT) given daily over 3 or 6 weeks with or without an oral chemotherapy. Radiation is targeted to the visible residual tumor on magnetic resonance imaging (MRI) images plus a large margin of 15 to 30 mm to account for possible cancer cells outside the visible tumor and for potential growth or shifts in tumor position throughout the prolonged RT course. Standard RT uses MRI to create a reference plan (with large margins) and treats that same volume every day. This exposes a large amount of healthy brain tissue to radiation leading to toxicity and reduced quality of life.

A new technology, the MR-Linac, combines an MRI scanner and a Linac (radiation delivery machine) into one unit. This allows for "adaptive" RT by obtaining an updated MRI scan each day just prior to treatment, adapting the RT plan to take into account any changes in the tumor or the patient's anatomy on that given day. This allows for a smaller (5 mm) margin on the visible tumor as its position can be tracked daily. The goal of this study is to use adaptive RT with small margins to demonstrate that the local control of the visible tumor is not compromised compared to the large volumes used with standard non-adaptive RT, while determining whether smaller margins lead to decreased radiation toxicity and therefore improved quality of life by minimizing radiation exposure.


Eligibility criteria: Inclusion Criteria:

* Patients aged 18 years and older
* Histopathologically confirmed malignant glioma of the brain, Grade 4 (GBM)
* Eligible for RT in 15 or 30 fractions with or without chemotherapy (temozolamide)
* Expected survival greater than 12 weeks
* WHO performance status less than or equal to 2
* Able to converse and answer questionnaires in English language
* Has a maximum final planning volume less than 150 cm3

Exclusion Criteria:

* Contraindications to MRI examination as per standard MRI screening policy
* Contraindication to Gadolinium-based contrast media
* Unable to lie flat in a supine position for 30 minutes
* Poor baseline kidney function with an eGFR \< 60 mL/min
* Unable to tolerate immobilization in a head thermoplastic mask
* Patients \>140 kg and/or a circumference \>60cm
* Previous cranial irradiation
* Infratentorial tumour extent, multifocal of leptomeningeal disease
* Unable to give informed consent

Primary outcomes:
measure: Imaging-detected tumor recurrence at the edge of the radiation volume ("marginal" failure)
timeFrame: Within 1 year from end of radiation
Secondary outcomes:
measure: Tumor volume changes during RT
timeFrame: 6 weeks
measure: Acute radiation toxicity based on RTOG/EORTC Common Toxicity Criteria
timeFrame: 6 weeks
measure: Quality of life changes based on EORTC QLQ-C30
timeFrame: 1 year
measure: Dexamethasone usage
timeFrame: 10 weeks
measure: Quality of life based on EORTC QLQ-BN20
timeFrame: 1 year
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
References: