UNIty-Based MR-Linac Guided Adaptive RadioThErapy for High GraDe Glioma-4

Official title

UNIty-Based MR-Linac Guided Adaptive RadioThErapy for High GraDe Glioma-4 (UNITED-4): Prospective Evaluation of FLAIR-Guided Clinical Target Volume Reduction

Overview

This study builds on the results of prior studies (UNITED and UNITED-3). The goal of UNITED-4 is to test whether an adaptive radiation therapy (RT) therapy approach ('dose painting'), with reduced margins, impacts approach in participants with glioblastoma impacts local control compared to standard non-adaptive RT approach. The main questions of the study are to see how this adaptive RT approach with reduced margins compares to standard RT in terms of: * Local control * Overall and progression-free survival * Patterns of failure * Toxicity, Neurological Function, and Quality of Life * Longitudinal imaging features

Detailed description

The UNITED-4 study is for people diagnosed with glioblastoma (GBM) or other high-grade (aggressive) brain tumors. These tumors are typically treated with radiation therapy combined with a chemotherapy agent called temozolomide. Standard radiation for these tumours uses a wide margin around the tumor to ensure that all areas potentially at risk for the presence of cancer cells are targeted, but this approach can also damage healthy brain tissue.

The UNITED-4 trial uses a new machine called an MR-Linac, which combines a radiation machine with an magnetic resonance imaging (MRI) scanner, allowing doctors to take daily images during treatment and adjust the radiation plan in real-time. This study will personalize treatment based on fluid-attenuated inversion recovery (FLAIR) MRI imaging that shows where cancer cells might be spreading while using smaller treatment margins to protect more of the normal brain. Patients will receive either 30 treatments over 6 weeks or 15 treatments over 3 weeks, with different radiation doses delivered simultaneously to high-risk areas (tumour) and lower-risk areas (normal brain). The goal of this study is to determine if this approach maintains cancer control while potentially reducing side effects and improving quality of life compared to standard treatments. Risks include radiation side effects (expected to be no worse than standard treatment) and a possibility of tumor recurrence at treatment edges.

The study will enroll 60 patients over 24 months at Sunnybrook Health Sciences Centre.

Interventions

• Radiation Dose painting + Reduced Margins
  Reduced margins using a dose painting approach

Primary outcome measures

• Disease worsening at 6 months [Time frame: From RT start to 6 months after RT]

Secondary outcome measures (7)

• Overall survival [Time frame: Throughout study participation, anticipated 0-25 months]
• Type of progression [Time frame: Throughout study participation, anticipated 0-25 months]
• Number of participants with RT-related adverse events as assessed by CTCAE v5.0 [Time frame: Throughout study participation, anticipated 0-25 months]
• Neurological Function [Time frame: Throughout study participation, anticipated 0-25 months]
• Imaging features as correlates of treatment outcomes [Time frame: Throughout study participation, anticipated 0-25 months]
• Changes in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) [Time frame: Throughout study participation, anticipated 0-25 months]
• Changes in the European Organisation for Research and Treatment of Cancer Brain Cancer Module (EORTC QLQ-BN20) [Time frame: Throughout study participation, anticipated 0-25 months]

Eligibility criteria

Inclusion criteria

• Histopathologically confirmed, based on biopsy or surgical resection, glioblastoma or WHO grade 4 astrocytoma (IDH wild type or mutant)
• Deemed clinically appropriate for concurrent chemoradiotherapy (with temozolomide) with definitive/radical intent
• Biopsy or surgical resection performed ≤ 12 weeks prior to study entry
• Expected survival ≥ 12 weeks
• ECOG performance status of 0, 1 or 2
• 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
• Patients with multifocal or multicentric disease will be allowed per the discretion of the radiation oncologist

Exclusion criteria

• Contraindications to MRI examination as per standard MRI screening policy
• Contraindication to Gadolinium-based contrast media
• Enhancing disease involving any part of the brainstem on post-gadolinium T1-weighted MRI imaging for patients being treated using the short-course 15-fraction regimen
• Inability to lie flat in a supine position for at least 30 minutes
• Inability to tolerate immobilization in a head thermoplastic mask
• Patients > 140 kg and/or a circumference > 60 cm (MRI scanner weight and bore size limits)
• Prior therapeutic cranial irradiation
• Leptomeningeal dissemination of disease
• History of other malignancies with the exception of adequately treated non-melanoma skin cancer, or curatively treated other solid tumours with no evidence of disease for ≥ 2 years
• Patients with any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 1 center

• Sunnybrook Health Sciences Centre - Odette Cancer Centre — Toronto

Identifiers

NCT: NCT07459101 · UNITED-4

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗