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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 3INTERVENTIONAL

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

Bevacizumab Versus Corticosteroids as First-line Treatment in Patients With Symptomatic Cerebral Radiation Necrosis After Radiation for High-grade Glioma or Brain Metastases (NCT06888817) is a Phase 3 interventional studying Radiation Necrosis and High Grade Glioma (III or IV), sponsored by The Netherlands Cancer Institute. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 3 trials confirm efficacy and safety in large patient groups (often 300–3,000+) and form the evidence base for an FDA approval submission. For Radiation Necrosis, Phase 3 studies typically randomize participants between the investigational treatment and either a placebo or current standard of care. A successful Phase 3 result is the threshold most treatments need to clear before regulatory approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

A target enrollment of 408 participants makes this a sizable late-stage trial. Studies in this range typically have enough power to detect clinically meaningful differences from a comparator and to characterize less-common side effects.

Who May Be Eligible (Plain English)

Who May Qualify: Inclusion all patients (both HGG and BM): 1. Age ≥ 18 years old 2. 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 3. KPS score ≤ 90 and a minimum loss of two points in at least one domain of the NANO scale as compared to the maximum score of at that domain due to sCRN 4. Maximum daily dexamethasone use of 1 mg/day for the 8 weeks preceding randomization 1. Dexamethasone may have been prescribed for various indications, except for managing (ongoing) cerebral edema 2. Higher doses of dexamethasone are permitted during the week immediately preceding randomization if used specifically for the treatment of sCRN 5. Able to understand the patient information, online tests and questionnaires 6. Written willing to sign a consent form Inclusion BM: 1\. BM of solid tumour, including all primary tumour types Inclusion HGG: 1\. 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 Who Should NOT Join This Trial: 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: 1. Prior treatment with bevacizumab \<6 months before diagnosis of sCRN 2. Life expectancy \<3 months 3. Impending radiological or clinical signs of brain herniation necessitating immediate decompressive surgery 4. Any comorbidity or condition that prevents safe administration of the studied medication, determined by the treating physician, including but not limited to: 1. Intolerance for murine proteins ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: Inclusion all patients (both HGG and BM): 1. Age ≥ 18 years old 2. 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 3. KPS score ≤ 90 and a minimum loss of two points in at least one domain of the NANO scale as compared to the maximum score of at that domain due to sCRN 4. Maximum daily dexamethasone use of 1 mg/day for the 8 weeks preceding randomization 1. Dexamethasone may have been prescribed for various indications, except for managing (ongoing) cerebral edema 2. Higher doses of dexamethasone are permitted during the week immediately preceding randomization if used specifically for the treatment of sCRN 5. Able to understand the patient information, online tests and questionnaires 6. Written informed consent Inclusion BM: 1\. BM of solid tumour, including all primary tumour types Inclusion HGG: 1\. 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 Exclusion Criteria: 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: 1. Prior treatment with bevacizumab \<6 months before diagnosis of sCRN 2. Life expectancy \<3 months 3. Impending radiological or clinical signs of brain herniation necessitating immediate decompressive surgery 4. Any comorbidity or condition that prevents safe administration of the studied medication, determined by the treating physician, including but not limited to: 1. Intolerance for murine proteins 2. Hypersensitivity or allergy to the active substance or to any of the excipients of bevacizumab or dexamethasone 3. 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. 4. 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 5. History of gastro-intestinal fistula, perforation or abscess \< 6 months 6. 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 7. Excess risk of bleeding * History or evidence of inherited bleeding diathesis or significant coagulopathy with the risk of bleeding * Decreased platelet count \< 75x109/L 8. Risk of wound healing complications * Significant non-healing wound, (peptic) ulcer or bone fracture * Major surgical procedure (including open biopsy) or significant traumatic injury within 28 days prior to first study treatment or planned surgical procedure within the following next 28 days after planned study inclusion * Minor surgical procedure, stereotactic/core biopsy, fine needle aspiration within 7 days prior to first study treatment 9. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hours urine collection and must demonstrate ≤ 1 g of protein/24 hr. 10. Previous, current or planned high dose radiotherapy in the abdomen 11. Pregnancy or lactation. Women of child bearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to randomization. WOCBP and female partners of male patients must comply with adequate contraception methods as requested by the study protocol 12. Evidence of any other medical conditions (such as psychiatric illness, physical examination or laboratory findings) that may interfere with the study treatment, affect patient compliance or place the patient at high risk for treatment-related complications according to the treating physician 13. Current or recent (within 30 days of first study treatment) treatment with another investigational drug or participation in another interventional study In case of uncertainty, consult the principal investigator of the study site.

Treatments Being Tested

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

Locations (5)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Netherlands Cancer Institute - Antoni van Leeuwenhoek
Amsterdam, Netherlands
Amsterdam University Medical Centers, location VUmc and AMC
Amsterdam, Netherlands
Leiden University Medical Center
Leiden, Netherlands
Haaglanden Medical Center
The Hague, Netherlands
University Medical Center Utrecht
Utrecht, Netherlands

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06888817), the sponsor (The Netherlands Cancer Institute), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06888817 clinical trial studying?

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… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06888817?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06888817?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06888817. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06888817. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.