Astrocytoma, Grade IV, Glioblastoma (GBM)
Conditions
Brief summary
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
RADIATIONDose painting + Reduced Margins
Reduced margins using a dose painting approach
Sponsors
Sunnybrook Health Sciences Centre
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease worsening at 6 months | From RT start to 6 months after RT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Throughout study participation, anticipated 0-25 months | — |
| Type of progression | Throughout study participation, anticipated 0-25 months | Whether the progression occurred at local, marginal, or distant location |
| Number of participants with RT-related adverse events as assessed by CTCAE v5.0 | Throughout study participation, anticipated 0-25 months | Acute (within 3 months of RT completion) and late (\> 3 months of RT completion) effects will be assessed |
| Neurological Function | Throughout study participation, anticipated 0-25 months | Will be assessed by your treating doctor, using the Neurological Assessment in Neuro-Oncology (NANO) scale |
| Imaging features as correlates of treatment outcomes | 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) | Throughout study participation, anticipated 0-25 months | This is one of the questionnaires that will be used to qualitatively assess the changes to your quality of life (neurological function, symptoms, and overall status), during your participation on the study. A higher scale score represents a higher response level with regards to the measured item. |
| Changes in the European Organisation for Research and Treatment of Cancer Brain Cancer Module (EORTC QLQ-BN20) | Throughout study participation, anticipated 0-25 months | This questionnaire is used together with QLQ-C30 to qualitatively assess changes in your symptoms during your participation on the study. A higher scale score represents more, or more severe, symptoms. |
Countries
Canada
Contacts
CONTACTHanbo Chen, MD
Outcome results
None listed