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

Sponsor
The Netherlands Cancer Institute
Study ID
NCT06888817
Phase
PHASE3
Status
Recruiting
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Conditions

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

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

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

Study Details

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.

Key Dates

First listed
Mar 21, 2025
Start date
Jun 19, 2025
Status verified
Feb 2026
Primary completion
Jul 31, 2028
Completion
Jul 31, 2030

Study Design

Enrollment
408 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Bevacizumab
    Intravenous bevacizumab at a 600 mg flat dose every three weeks for four courses over 12 weeks
  • Active Comparator: Dexamethasone
    Daily oral dexamethasone followed by a protocol-based tapering dose over 12 weeks

Primary Outcome Measure

Clinical efficacy, defined as ≤ 1.5mg dexamethasone/day with one of the following 1) an improved KPS (of ≥ 10 points ) + at least stable NANO or 2) improved NANO (of ≥ 2 points) + at least stable KPS [ Time Frame: 12 weeks ]

Central Contacts

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