Actively Recruiting

Phase 3
Age: 18Years +
All Genders
NCT06888817

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

Led by The Netherlands Cancer Institute · Updated on 2026-02-25

408

Participants Needed

5

Research Sites

262 weeks

Total Duration

On this page

Sponsors

T

The Netherlands Cancer Institute

Lead Sponsor

U

UMC Utrecht

Collaborating Sponsor

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

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

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age 18 years or older
  • First episode of symptomatic cerebral radiation necrosis at least 3 months after completion of focal (re-)irradiation
  • Diagnosis confirmed by local Neuro-Oncology Board with no tumor progression
  • Karnofsky Performance Score (KPS) of 90 or lower and minimum loss of two points in at least one domain of the NANO scale due to cerebral radiation necrosis
  • Maximum daily dexamethasone use of 1 mg/day for 8 weeks before randomization (except in the week before randomization if used for cerebral radiation necrosis)
  • Ability to understand patient information, online tests, and questionnaires
  • Provided written informed consent
  • For brain metastases patients: diagnosis of solid tumor brain metastases
  • For high-grade glioma patients: confirmed histological diagnosis according to WHO 2021 criteria including specific glioma subtypes
Not Eligible

You will not qualify if you...

  • Prior bevacizumab treatment within 6 months before diagnosis of symptomatic cerebral radiation necrosis
  • Life expectancy less than 3 months
  • Signs of brain herniation requiring immediate decompressive surgery
  • Any condition preventing safe medication administration, including intolerance or allergy to study drugs
  • Nephrotic syndrome or abnormal kidney function with creatinine clearance below 30 mL/min or significant proteinuria
  • Significant cardiovascular disease such as uncontrolled hypertension despite treatment, recent vascular events, heart failure NYHA II-IV
  • History of gastrointestinal fistula, perforation, or abscess within 6 months
  • Recent bleeding events including pulmonary hemorrhage, gastrointestinal bleeding, or recent intracranial hemorrhage
  • Increased risk of bleeding due to inherited conditions or low platelet count below 75x10^9/L
  • Risk of wound healing complications including recent major surgery or trauma within 28 days or minor procedures within 7 days before treatment
  • Previous, current, or planned high dose abdominal radiotherapy
  • Pregnancy or lactation without negative pregnancy test and required contraception
  • Other medical or psychiatric conditions interfering with treatment or compliance
  • Participation in another investigational drug study within 30 days before treatment

AI-Screening

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Trial Site Locations

Total: 5 locations

1

Netherlands Cancer Institute - Antoni van Leeuwenhoek

Amsterdam, Netherlands, 1066 CX Amsterdam

Actively Recruiting

2

Amsterdam University Medical Centers, location VUmc and AMC

Amsterdam, Netherlands

Actively Recruiting

3

Leiden University Medical Center

Leiden, Netherlands, 2333 ZA Leiden

Actively Recruiting

4

Haaglanden Medical Center

The Hague, Netherlands, 2262 BA Leidschendam

Actively Recruiting

5

University Medical Center Utrecht

Utrecht, Netherlands, 3584 CX Utrecht

Actively Recruiting

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Research Team

D

Danique Laan, MSc

CONTACT

D

Dieta Brandsma, MD, PhD

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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