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

Recruiting now · Phase 3

Conditions studied: Radiation Necrosis, High Grade Glioma (III or IV), Brain Metastasases, Radiation Toxicity, Radiation Effect, Radiation Injury, Radiation Injuries

In brief

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 facts

Study ID: NCT06888817
Run by: The Netherlands Cancer Institute
People needed: 408
Starts: 2025-06-19
Expected to finish: 2030-07-01
Last updated by the study team: 2026-07-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Inclusion all patients (both HGG and BM):
Age ≥ 18 years old
First episode of sCRN ≥ 3 months after completion of focal (re-)irradiation, as determined by the local Multidisciplinary Neuro-Oncology Board. A clear working diagnosis of CRN without evidence of a combination with tumour progression is required
KPS score ≤ 90 and either (a) a minimum loss of two points in at least one domain of the Neurologic Assessment in Neuro-Oncology (NANO) scale as compared to the maximum score of that domain due to sCRN, or (b) a headache attributable to sCRN with an average intensity ≥5/10 on the NRS, persisting for ≥10 consecutive days, with inadequate relief despite an adequate trial of paracetamol and/or an NSAID unless these medications are contra-indicated or not tolerated
Maximum daily dexamethasone use of 1 mg/day for the 8 weeks preceding randomization
Dexamethasone may have been prescribed for various indications, except for managing (ongoing) cerebral edema
Higher doses of dexamethasone are permitted 3 weeks immediately preceding randomization if used specifically for the treatment of sCRN
Able to understand the patient information, online tests and questionnaires
Written informed consent
Inclusion BM:
BM of solid tumour, including all primary tumour types
Inclusion HGG:
A confirmed histological diagnosis of high-grade diffuse glioma according to WHO 2021 criteria, including: astrocytoma, IDH-mutant, grade 3-4; astrocytoma, IDH-wildtype (sybtype molecular glioblastoma); oligodendroglioma, 1p/19q codeleted, grade 3; diffuse glioma, NEC, grade 3-4; or glioblastoma, IDH-wildtype, grade 4

You may not qualify if…

A potential subject who meets any of the following criteria will be excluded from participation in this study, both for the BM and HGG group:
Prior treatment with bevacizumab <6 months before diagnosis of sCRN
Life expectancy <3 months
Impending radiological or clinical signs of brain herniation necessitating immediate decompressive surgery
Any comorbidity or condition that prevents safe administration of the studied medication, determined by the treating physician, including but not limited to:
Intolerance for murine proteins
Hypersensitivity or allergy to the active substance or to any of the excipients of bevacizumab or dexamethasone
Nephrotic syndrome or abnormal renal function
o Calculated (Cockcroft-Gault) or measured creatinine clearance <30 mL/min; urine dipstick for proteinuria ≥ 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hours urine collection and must demonstrate ≤ 1 g of protein/24 hr.
Clinical significant cardiovascular disease
Uncontrolled hypertension (systolic BP >150mmHg and/or diastolic >100mmHg) despite the use of ≥ 3 antihypertensive drugs
Previous hypertensive crisis, hypertensive encephalopathy or previous reversible posterior leukoencephalopathy syndrome (RPLS)
Non tumour related vascular event (e.g. cerebral or cardiac ischemia/bleeding (including transient ischemic attack, cerebral ischemia, unstable angina or angina requiring intervention, myocardial infarction), peripheral arterial thrombus, peripheral artery disease, deep venous thrombosis, lung embolism) < 6 months
History of aortic aneurysm or dissection
Congestive heart failure NYHA II-IV
History of gastro-intestinal fistula, perforation or abscess < 6 months
History of bleeding
Relevant pulmonary hemorrhage/ hemoptysis < 1 month or the presence of a pulmonary lesion with a high risk of bleeding (= central lung tumour and/or untreated squamous cell carcinoma) according to the treating physician
Active gastrointestinal bleeding < 6 months
Evidence of recent intracranial hemorrhage on MRI brain <3 months. Asymptomatic presence of hemosiderin depositions or punctate hemorrhage in the tumour do not serve as a ground for exclusion
Excess risk of bleeding
History or evidence of inherited bleeding diathesis or significant coagulopathy with the risk of bleeding
Decreased platelet count < 75x109/L
Risk of wound healing complications
Significant non-healing wound, (peptic) ulcer or bone fracture

Where it is running

Netherlands Cancer Institute - Antoni van Leeuwenhoek — Amsterdam, Netherlands (enrolling)
Amsterdam University Medical Centers, location VUmc and AMC — Amsterdam, Netherlands (enrolling)
Leiden University Medical Center — Leiden, Netherlands (enrolling)
Haaglanden Medical Center — The Hague, Netherlands (enrolling)
University Medical Center Utrecht — Utrecht, Netherlands (enrolling)
Maastricht University Medical Center+ — Maastricht, Netherlands

Full record on ClinicalTrials.gov

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