UNIty-Based MR-Linac Guided Adaptive RadioThErapy for High GraDe Glioma-3 (UNITED-3) (UNITED-3)

UNIty-Based MR-Linac Guided Adaptive RadioThErapy for High GraDe Glioma-3 (UNITED-3): Applying a Two Phase, Personalized Margin, Reduced Clinical Target Volume Approach

The goal of this study is to test whether an adaptive radiation therapy (RT), two-phase 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, two-phase RT approach compares to standard RT in terms of:

• Local control
• Overall and progression-free survival
• Patterns of failure
• Toxicity, Neurological Function, and Quality of Life

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma Multiforme, Adult
• Intervention / Treatment: Radiation: Adaptive, two-phase RT

Detailed Description

Glioblastoma (GBM) is a high grade glioma (brain tumor) that is treated with surgery or biopsy followed by radiotherapy (RT) given daily over 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 with a two-phase approach to test the impact on local control of the visible tumor compared to the large volumes used with standard non-adaptive RT, as well as impacts on neurocognitive function and quality of life.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jay Detsky, MD; Phone Number: 4806 416-480-6100; Email: jay.detsky@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N3M5
      • Recruiting
      • SunnyBrook Health Sciences Centre
      • Contact: Jay Detsky, MD; Phone Number: 416-480-4806; Email: jay.detsky@sunnybrook.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histopathologically confirmed, based on biopsy or surgical resection, glioblastoma, or grade 4 astrocytoma, as defined by the World Health Organization (WHO)
• Deemed clinically appropriate for long course radiation therapy concurrent with systemic therapy
• Biopsy or surgical resection performed ≤ 12 weeks prior to study entry

• Adequate hematological, renal and hepatic functions as defined by the following required laboratory values obtained within 14 days prior to study entry:

  • Absolute granulocyte count (AGC) > 1.5 x 109/L (1,500 cells/mm3)
  • Platelet count > 100x109/L (100,000 cells/mm3)
  • Serum creatinine < 1.5 times the upper limit of normal
  • Total serum bilirubin < 1.5 times the upper limit of normal
  • Alanine Aminotransferase (ALT, or formerly serum glutamic-pyruvic transaminase (SGPT)) < 2.5 times the upper limit of normal
  • and/or aspartate aminotransferase (AST, or serum glutamic-oxaloacetic transaminase (SGOT)) < 2.5 times the upper limit of normal
• Expected survival ≥ 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Able (sufficiently fluent in English) and willing to complete quality of life 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 examination as per standard MRI screening policy
• Contraindication to Gadolinium-based contrast media
• 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
• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adaptive, two-phase RT	Radiation: Adaptive, two-phase RT; Participants in this arm will be treated with an adaptive, two-phase radiation therapy approach

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of marginal failure (if 20-80% of the recurrent GTV (rGTV) falls within the 95% isodose line)	Through study completion, anticipated 6-12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		Through study completion, anticipated 6-24 months
Progression-free survival		Through study completion, anticipated ~5 months
Rate of local control, in accordance with RANO-HGG criteria		Through study completion, anticipated ~5 months
Patterns of failure		Through study completion, anticipated 6-24 months
Rate of toxicity	Assessed using the Radiation Therapy Oncology Group (RTOG) acute toxicity scale, which assesses acute toxicity using a scale of 0-5, and late toxicity using a scale of 1-4. In both scales, a higher score means a worse outcome.	Through study completion, anticipated 6-24 months
Health-related Quality of Life	Assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 to measure quality of life	Through study completion, anticipated 6-24 months
Changes in neurologic function	Assessed through the Neurologic Assessment in Neuro-Oncology (NANO) scale	Through study completion, anticipated 6-24 months
Adaptive Radiation Dosimetry		6 weeks
Functional Imaging Kinetics as a Correlate of Treatment Response		Through study completion, anticipated 12-24 months

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: January 6, 2023
• First Submitted That Met QC Criteria: February 8, 2023
• First Posted (Actual): February 9, 2023

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: UNITED-3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No