UNIty-Based MR-Linac Guided AdapTive RadiothErapy for High GraDe Glioma: a Phase 2 Trial (UNITED)

UNIty-Based MR-Linac Guided AdapTive RadiothErapy for High GraDe Glioma: a Phase 2 Trial (UNITED Trial)

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.

Study Overview

• Status: Completed
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Radiation: Reduced margin adaptive radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N3M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Imaging-detected tumor recurrence at the edge of the radiation volume ("marginal" failure)	The presence of tumor on contrast-enhanced MRI between 1-2 cm from the edge of the treated radiation volume (commonly known as a marginal failure) within 1 year from radiation.	Within 1 year from end of radiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor volume changes during RT	Change in gross tumor volume (%) from start to end of RT	6 weeks
Acute radiation toxicity based on RTOG/EORTC Common Toxicity Criteria	Grades 1-4 toxicity during RT in the following categories: skin, CNS, eye, ear, and hematological	6 weeks
Quality of life changes based on EORTC QLQ-C30	Changes in quality of life during and after RT based on accepted EORTC cancer quality of life instruments administered each week on RT, 1 month post RT, and every 3 months subsequently	1 year
Dexamethasone usage	Amount of dexamethasone required during RT	10 weeks
Quality of life based on EORTC QLQ-BN20	Changes in quality of life during and after RT based on accepted EORTC brain tumor quality of life instruments administered each week on RT, 1 month post RT, and every 3 months subsequently	1 year

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2021
• Primary Completion (Actual): May 15, 2024
• Study Completion (Actual): May 15, 2024

Study Registration Dates

• First Submitted: January 19, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): January 27, 2021

Study Record Updates

• Last Update Posted (Actual): November 29, 2024
• Last Update Submitted That Met QC Criteria: November 26, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: 3412

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No