UNIty-Based MR-Linac Guided AdapTive RadiothErapy for High GraDe Glioma: A Phase 2 Trial

Glioblastoma Multiforme Clinical Trial

— UNITED  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04726397
• Other study ID #: 3412
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 29, 2021
• Est. completion date: May 2024

Study information

• Verified date: April 2023
• Source: Sunnybrook Health Sciences Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 108
• Est. completion date: May 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Radiation:
• Reduced margin adaptive radiotherapy
Reduced (5 mm) clinical target volume margin with weekly contrast-enhanced adaptive radiation on the MR-Linac treatment machine

Locations

Country	Name	City	State
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Tumor volume changes during RT	Change in gross tumor volume (%) from start to end of RT	6 weeks
Secondary	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
Secondary	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
Secondary	Dexamethasone usage	Amount of dexamethasone required during RT	10 weeks
Secondary	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