NCT06888817

Bevacizumab Versus Corticosteroids as First-line Treatment in Patients With Symptomatic Cerebral Radiation Necrosis After Radiation for High-grade Glioma or Brain Metastases

Bevacizumab for the Treatment of Cerebral RAdiation Induced NecrosiS (BRAINS) Study: a Multicenter, Open-label, Randomized Clinical Trial to Assess the Clinical Efficacy and Cost-effectiveness of Bevacizumab Versus Corticosteroids as First-line Treatment in Patients With Symptomatic Cerebral Radiation Necrosis After Radiation for High-grade Glioma or Brain Metastases

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 408 (estimated)
• Sponsor: The Netherlands Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Cerebral radiation necrosis (CRN) is a severe complication of high-dose radiation for brain metastases (BM) or glioma, which can potentially cause significant neurologic symptoms leading to serious morbidity and impaired quality of life (QoL). The first-line therapy for symptomatic CRN (sCRN) is corticosteroids, primarily dexamethasone, which often leads to complications, refractory symptoms, and interference with anti-cancer treatment. Since 2017, bevacizumab, an antibody against Vascular Endothelial Growth Factor (VEGF), has been used in a second-line treatment setting for refractory sCRN. A small randomized clinical trial (RCT) has shown that bevacizumab significantly diminishes cerebral edema on MRI and decreases clinical symptoms of sCRN in irradiated glioma patients. Several non-randomized clinical studies demonstrated a beneficial radiological and clinical effect of bevacizumab in patients with sCRN after irradiation for BM. The optimal first-line treatment for sCRN is currently unknown. Effective and safe first-line treatment of sCRN will optimize the patient's well-being and health-related QoL. Furthermore, minimizing corticosteroid use will benefit the clinical treatment options and outcomes of concomitant or future anti-cancer treatment. This phase III multicenter, open-label, randomized clinical trial compares the clinical efficacy of first-line bevacizumab versus standard-of-care dexamethasone for sCRN in patients with high-grade glioma (HGG) or BM.

Detailed description

The primary objective of this trial is to compare the clinical efficacy of first-line bevacizumab versus dexamethasone for sCRN in HGG and BM patients at 12 weeks. Both patients with HGG and patients with BM will be randomly assigned in a 1:1 ratio to one of two following treatment arms. ARM 1 Intervention arm: intravenous bevacizumab at a 600 mg flat dose every three weeks for four courses over 12 weeks at hospital daycare. ARM 2 Control arm: daily oral dexamethasone followed by a protocol-based tapering dose over 12 weeks. Patients in the intervention (bevacizumab) arm may use dexamethasone concurrently with bevacizumab if clinically indicated. The study treatment will be administered over 12 weeks, with a follow-up period of 2 years. Patients in both arms will have regular inpatient hospital visits and MRI brain scans, complete the Amsterdam Cognition scan twice during treatment, complete QoL, epilepsy, productivity, and medical costs questionnaires during treatment and follow up, and undergo optional blood withdrawal for translational research purposes. Standard of care laboratory blood tests during treatment depend on the treatment arm.

Conditions

• Radiation Necrosis
• High Grade Glioma (III or IV)
• Brain Metastasases
• Radiation Toxicity
• Radiation Effect
• Radiation Injury
• Radiation Injuries

Interventions

Type	Name	Description
DRUG	Bevacizumab	Intravenous bevacizumab at a 600 mg flat dose every three weeks for four courses over 12 weeks
DRUG	Dexamethasone	Daily oral dexamethasone followed by a protocol-based tapering dose over 12 weeks

Timeline

• Start date: 2025-06-19
• Primary completion: 2028-07-01
• Completion: 2030-07-01
• First posted: 2025-03-21
• Last updated: 2026-02-25

Locations

5 sites across 1 country: Netherlands