Achieving a Better Outcome Through Limiting the Glioblastoma Clinical Target Volume

Not Applicable

Not yet recruiting

• Conditions: Glioblastoma; Radiotherapy Side Effect

• Registration Number: NCT06719440
• Lead Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Brief Summary

The objective of the BELGICA trial is to evaluate if radiotherapy could be given in a more focused manner in patients with glioblastoma in order to reduce side effects and improve quality of life.

The glioblastoma (GBM) is the most common and aggressive tumour originating from the brain, affecting approximately 600 patients per year in Belgium. The treatment consists in surgical resection of the tumour (when feasible), followed by a combination of radiotherapy and chemotherapy. Despite multimodal treatment (surgery, radiotherapy, and chemotherapy), the life expectancy of patients with GBM remains limited, with an average survival of 12-18 months and only 5% of patients surviving more than 5 years. In addition to limited survival, most patients with GBM experience impaired quality of life, both because of the disease and treatments.

Radiotherapy is a treatment where radiation is used to kill cancer cells. In GBM, radiotherapy is targeted at the tumour (or tumour bed if the tumour was resected) with a safety margin around it (the "Clinical Target Volume" or CTV) to account for potential microscopic spread of the tumour. The downside of this safety margin is that a substantial amount of brain tissue is irradiated, which can lead to treatment toxicity. Reducing the CTV margin would enable to decrease the volume of brain being irradiated and could thereby allow to reduce the side effects of brain irradiation.

The BELGICA trial (Achieving a BEtter outcome through Limiting the GlIoblastoma Clinical tArget volume) is a national multicentre trial which will evaluate if reducing the irradiation volume in glioblastoma is safe and allows for lowering side effects and improving quality of life.

Detailed Description

INDICATION :

Patients with newly diagnosed glioblastoma for whom radiochemotherapy is indicated

RATIONALE :

Glioblastoma is the most frequent primary malignant brain tumour, annually affecting approximately 600 patients in Belgium.

The current management of glioblastoma includes surgical resection (when feasible), followed by radiotherapy (RT) and chemotherapy. Despite this multimodal treatment, the prognosis of patients with glioblastoma is dismal with a median overall survival of approximately 1 year.

In addition to poor survival, patients with glioblastoma face several symptoms, notably cognitive decline and deterioration in quality of life (QOL), which are both resulting from the disease evolution and the treatments. Given the limited life expectancy of these patients, improvement of well-being during the remaining survival period is essential and is a major concern for glioblastoma patients and their relatives.

In glioblastoma, radiotherapy is targeted at the tumour (or tumour bed after resection) with a safety margin around it (i.e., the "Clinical Target Volume" or CTV) to account for potential microscopic extension of the tumour. The downside of this safety margin is that a substantial amount of normal brain tissue is irradiated, which can lead to treatment toxicity. Reducing the CTV margin would enable to decrease the volume of brain being irradiated and could thereby allow to reduce the side effects of brain irradiation.

Current European guidelines in glioblastoma recommend a clinical target volume (CTV) margin of 15 mm around the tumour. However, the optimal target volume is still unknown, mainly based on historical practices, and different margins have been used in clinical practice.

The BELGICA trial will prospectively evaluate if reducing the CTV margin from 15 to 10 mm allows for improving the toxicity profile of the treatment without compromising the outcome.

This intervention is expected to be safe and to reduce toxicity based on available clinical data.

Target volume reduction in glioblastoma Several retrospective or prospective non-randomized series of patients treated with a \<= 10 mm CTV margin showed local control and survival outcomes similar to those of patients treated with larger margins, which supports the safety of the intervention. Similarly, pattern of recurrence analysis in patients treated with a \>= 15 mm CTV suggests that using a 10 mm CTV margin would not lead to more recurrences.

Relation between radiation dose and toxicity in glioblastoma Current clinical data in patients with glioblastoma show that lower radiation dose to surrounding normal brain structures is associated with lower cognitive decline, improved QOL, reduced toxicity and fatigue.

Glioblastoma, radiotherapy, and cognitive decline Most patients with glioblastoma present with neurocognitive dysfunction at the time of diagnosis and will experience further progressive decline during the clinical course of the disease. This occurs early, with a median time to deterioration of approximately 1 months .

Neurocognitive decline is multifactorial, due to tumour-, patient-, and treatment-related factors.

Cranial irradiation is associated with cognitive toxicity. In patients with brain metastases, strategies aiming to reduce the radiation dose to the surrounding brain structures have allowed to reduce the rate of cognitive decline, e.g. hippocampal-avoidance in patients receiving whole-brain radiotherapy.

By reducing the irradiation volume in patients with glioblastoma, the dose to the surrounding brain structures will be lowered, potentially reducing the rate of cognitive decline.

METHODS :

The BELGICA trial will include 347 patients in Belgium with newly diagnosed glioblastoma. The patients will be randomized 1:1 into two groups. The experimental group will receive a radiotherapy with a reduced irradiation volume (CTV 10mm). The control group will receive radiotherapy with standard irradiation volume (CTV 15mm). In both groups, patients will receive temozolomide chemotherapy in association with radiotherapy. Stratification factors are: age (under/above 70 years), MGMT promotor methylation status (methylated/unmethylated/unknown), and extent of resection.

Study Timeline

• Study First Submitted: 2024-11-15
• Study First Submitted QC: 2024-12-03
• Study First Posted: 2024-12-05
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-18
• Last Update Posted: 2025-04-23
• Study Start: 2025-05-12
• Primary Completion: 2031-10
• Study Completion: 2031-10

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 347

Inclusion Criteria

• Participants capable of giving informed consent
• Age >= 18 y.o.
• WHO performance status 0-2
• Newly diagnosed glioblastoma (Histologically proven glioblastoma per WHO 2021 classification based on biopsy or resection )
• Indication of chemoradiotherapy confirmed by multidisciplinary tumour board

Exclusion Criteria

• Participation in a competing trial
• Known contraindication to undergo MRI scans

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Overall Survival	From randomization to the end of the study	Number of days from date of randomization to the date of death due to any cause

Secondary Outcome Measures

Name	Time	Method
Neurocognitive functioning	at baseline, 1 month after radiotherapy and at 1 year	Hopkins verbal learning test revised; Trail Marking Test A \& B; Controlled Oral Word Association Test
Health-related Quality of Life	From enrollment until end of follow-up (2 years)	EQ-5D-5L; QLQ-C30; QLQ-BN20
Progression-free survival	From randomization until end of follow-up (2 years)	Length of time during and after treatment for a disease, such as cancer, that a patient lives with the disease without it worsening
Pattern of recurrence	From randomization until end of follow-up (2 years)	(in case of progression) Manner in which the tumor returns after a period of improvement or remission. It often involves tracking the frequency, timing, and location of the tumor's return
Anti-edema therapy	From randomization until end of follow-up (2 years)	Recording of the needs of anti-edema therapy
Radiation-induced toxicity	From enrollment until end of follow-up (2 years)	Assessment of fatigue, headache, nausea, alopecia and radiatio dermatitis according to the CTCAE assessment score. Score ranges from Grade 1 to Grade 5, with higher grades resulting in more severe symptoms.

Trial Locations

Locations (23)

AZ Sint Jan; 🇧🇪 Brugge, Belgium

Cliniques universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

Institut Jules Bordet; 🇧🇪 Bruxelles, Belgium

UZ Brussel; 🇧🇪 Bruxelles, Belgium

Ziekenhuis Oost-Limburg (ZOL); 🇧🇪 Genk, Belgium

AZ Sint-Lucas; 🇧🇪 Gent, Belgium

UZ Gent; 🇧🇪 Gent, Belgium

Grand Hôpital de Charleroi; 🇧🇪 Gilly, Belgium

JESSA Ziekenhuis; 🇧🇪 Hasselt, Belgium

AZ Groeninge; 🇧🇪 Kortrijk, Belgium

Olv Azorg; 🇧🇪 Aalst, Belgium

EpiCURA; 🇧🇪 Baudour, Belgium

Chu Helora; 🇧🇪 La Louvière, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

CHU Liège; 🇧🇪 Liège, Belgium

AZ Sint Maarten; 🇧🇪 Mechelen, Belgium

Hôpital André Vésale - HUmani; 🇧🇪 Montigny-Le-Tilleul, Belgium

CH Mouscron; 🇧🇪 Mouscron, Belgium

CHU UCL Namur - Sainte Elisabeth; 🇧🇪 Namur, Belgium

AZ Delta; 🇧🇪 Roeselare, Belgium

Cliniques de l'Europe; 🇧🇪 Uccle, Belgium

CHR Verviers; 🇧🇪 Verviers, Belgium

ZAS Augustinus; 🇧🇪 Wilrijk, Belgium