2024-512466-34-00招募中3 期
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
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting5 个研究点 分布在 1 个国家目标入组 408 人开始时间: 2025年2月18日最近更新:
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 408
- 试验地点
- 5
- 主要终点
- a favourable clinical response, which is defined as (a) utilization of 1.5mg/day or less dexamethasone and (b) meeting one of the following two criteria: 1) improved Karnofsky Performance Status (KPS) (≥ 10 points ) + at least stable Neurologic Assessment in Neuro-Oncology (NANO) or 2) improved NANO (≥ 2 points) + at least stable KPS, assessed 12 weeks after initiation of treatment.
研究概览
简要总结
To compare the clinical efficacy of first-line bevacizumab vs dexamethasone for cerabral radiation necrosis (sCRN) in high grade glioma (HGG) and brain metastases (BM) patients
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years old
- •First episode of sCRN ≥ 3 months after completion of focal (re-)irradiation, as determined by the local Multidisciplinary Brain Tumour Board. A clear working diagnosis of CRN without evidence of mixed tumour progression is required
- •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
- •Maximum daily dexamethasone use of 1 mg/day for the 8 weeks preceding randomization a. Dexamethasone may have been prescribed for various indications, except for managing (ongoing) cerebral edema b. Higher doses of dexamethasone are permitted during the week immediately preceding randomization if used specifically for the treatment of sCRN
- •Able to understand the patient information, online tests and questionnaires
- •Written informed consent
- •Only for BM patients: BM of solid tumour, including all primary tumour types
- •Only for HGG patients: 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
排除标准
- •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: a. Intolerance for murine proteins b. Hypersensitivity or allergy to the active substance or to any of the excipients of bevacizumab or dexamethasone c. Nephrotic syndrome or abnormal renal function - Calculated (Cockcroft-Gault) or measured creatinine clearance < urine dipstick for proteinuria ≥ 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hours urine c30 mL/min;ollection and must demonstrate ≤ 1 g of protein/24 hr. d. Clinical significant cardiovascular disease o Uncontrolled hypertension (systolic BP >150mmHg and/or diastolic >100mmHg) despite the use of ≥ 3 antihypertensive drugs o Previous hypertensive crisis, hypertensive encephalopathy or previous reversible posterior leukoencephalopathy syndrome (RPLS) o 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 o History of aortic aneurysm or dissection o Congestive heart failure NYHA II-IV e. History of gastro-intestinal fistula, perforation or abscess < 6 months f. History of bleeding o 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 o Active gastrointestinal bleeding < 6 months o 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 g. Excess risk of bleeding o History or evidence of inherited bleeding diathesis or significant coagulopathy with the risk of bleeding o Decreased platelet count < 75x109/L h. Risk of wound healing complications o Significant non-healing wound, (peptic) ulcer or bone fracture o 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 o Minor surgical procedure, stereotactic/core biopsy, fine needle aspiration within 7 days prior to first study treatment i. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hours urine collection and must demonstrate ≤ 1 g of protein/24 hr. j. Previous, current or planned high dose radiotherapy in the abdomen k. 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 (Paragraph 8.2.1 Pregnancy, contraception and breastfeeding) l. 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 m. Current or recent (within 30 days of first study treatment) treatment with another investigational drug or participation in another interventional study
结局指标
主要结局
a favourable clinical response, which is defined as (a) utilization of 1.5mg/day or less dexamethasone and (b) meeting one of the following two criteria: 1) improved Karnofsky Performance Status (KPS) (≥ 10 points ) + at least stable Neurologic Assessment in Neuro-Oncology (NANO) or 2) improved NANO (≥ 2 points) + at least stable KPS, assessed 12 weeks after initiation of treatment.
a favourable clinical response, which is defined as (a) utilization of 1.5mg/day or less dexamethasone and (b) meeting one of the following two criteria: 1) improved Karnofsky Performance Status (KPS) (≥ 10 points ) + at least stable Neurologic Assessment in Neuro-Oncology (NANO) or 2) improved NANO (≥ 2 points) + at least stable KPS, assessed 12 weeks after initiation of treatment.
次要结局
- improvement of ≥10 points on the EORTC QLQ C30 physical functioning (and other clinically relevant functioning and symptom scales) at 12 weeks
- reduction of cerebral edema on T2/Fluid Attenuated Inversion Recovery (FLAIR) and contrast-enhancing lesion on Based on CCMO protocol template CTR Version 3.0, May 2023 14 of 103 T1 MRI at 12 weeks
- change in cognitive functioning measured by the Amsterdam Cognition Scan (ACS) at 12 weeks
- experienced epileptic seizure frequency and antiseizure medication use at 12 weeks
- number of treatment related adverse events until 21 days post end of treatment
- 2-year sCRN recurrence free survival
- time to next anti-CRN treatment
- 2-year progression free survival
- 2-year overall survival
- the cost-effectiveness of both treatments
- the number of patients who reached the main endpoint between 2 and 4 cycles of bevacizumab
研究者
Dr. D. Brandsma
Scientific
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
研究点 (5)
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