A Randomized Trial of Steroid Avoidance, Dexamethasone, and RAGE Inhibition for Perioperative Cerebral Edema Management in High-Grade Gliomas
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- change in peritumoral edema between the preoperative and postoperative period
研究概览
简要总结
The purpose of this study is to learn whether two alternatives to standard steroid treatment can safely control swelling around a brain tumor after surgery. The study will compare three approaches by placing participants in one of three study groups: standard dexamethasone (a steroid), no routine steroid treatment, and azeliragon, a study drug that may reduce brain swelling through a different pathway. Researchers want to determine whether these alternatives can control swelling while reducing some of the side effects associated with steroid use.
Participants in this study will be randomly assigned to one of three study groups. Participants will undergo their planned brain tumor surgery and receive the treatment assigned to their group. Study procedures are the same as their routine care and include physical and neurological examinations, blood tests, MRI scans, review of medical records, and collection of tumor tissue removed during surgery (optional). Most study visits will occur during routine medical care. Participants will be followed for approximately 24 months after surgery.
详细描述
This study is a randomized Phase II trial because it is designed to evaluate the preliminary efficacy, safety, and feasibility of steroid avoidance and azeliragon as alternatives to dexamethasone for perioperative cerebral edema management in high-grade glioma. The trial uses an intermediate imaging-based efficacy endpoint, enrolls a modest sample size, and is intended to identify promising strategies for subsequent confirmation in a definitive Phase III study.
The trial compares three perioperative strategies-standard dexamethasone, complete steroid avoidance, and RAGE inhibition with azeliragon-to determine their relative safety and effectiveness in controlling cerebral edema following tumor resection. In addition to edema control, the study evaluates clinical, functional, and immunologic outcomes associated with perioperative corticosteroid exposure.
Despite widespread use, dexamethasone lacks prospective evidence defining its optimal perioperative role in glioma patients. This study addresses that gap by rigorously evaluating steroid avoidance and a mechanistically targeted alternative, with the goal of improving patient outcomes while minimizing treatment-related toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years at the time of screening
- •Newly diagnosed supratentorial tumor with imaging characteristics consistent with high-grade glioma
- •Candidate for craniotomy with planned resection of more than 50% of the contrast-enhancing tumor
- •Midline shift ≤10 mm on preoperative imaging
- •Limited pre-enrollment corticosteroid exposure (≤10 mg dexamethasone total and no chronic steroid use within 30 days)
- •Karnofsky Performance Status ≥60
- •Adequate organ function to undergo surgery and postoperative care as determined by the investigator
- •Ability to provide informed consent and comply with study procedures
- •Agreement to use effective contraception, when applicable
排除标准
- •Participants meeting any of the following will be excluded:
- •Imaging or clinical features highly suggestive of primary CNS lymphoma or metastatic disease
- •Posterior fossa tumors or lesions associated with high risk of brainstem compression
- •Leptomeningeal or widely disseminated disease
- •Clinical conditions requiring immediate corticosteroid therapy
- •Prior exposure to high-dose corticosteroids (>10 mg dexamethasone) or chronic steroid use within 30 days
- •Active systemic illness that increases surgical risk, including uncontrolled infection, coagulopathy, or severe cardiopulmonary disease
- •Pregnancy or breastfeeding
- •Known immunodeficiency or chronic infection requiring immunosuppressive therapy
- •Use of investigational agents within 30 days or concurrent use of immunosuppressive medications not permitted by protocol
- •Known hypersensitivity to azeliragon
- •Inability to undergo MRI due to contraindications such as incompatible implants or severe claustrophobia
- •Life expectancy less than 3 months as determined by the investigator
- •Participation in another interventional clinical trial prior to initiation of standard adjuvant therapy Vulnerable Populations: This study will not enroll children, pregnant or breastfeeding individuals, or prisoners. Individuals with impaired decision-making capacity may be enrolled only when a legally authorized representative is available to provide consent in accordance with institutional and regulatory requirements.
结局指标
主要结局
change in peritumoral edema between the preoperative and postoperative period
时间窗: before the start of adjuvant chemo radiation (up to 6 weeks)
The primary outcome is the change in peritumoral edema between the preoperative and postoperative period. Specifically, it is the ratio of postoperative to preoperative peritumoral edema volume, adjusted for extent of enhancing tumor removed. This outcome is derived from MRI-based volumetric assessment and reflects the effectiveness of each perioperative strategy in controlling cerebral edema while accounting for surgical factors
次要结局
未报告次要终点
研究者
Akshitkumar MIstry
Assistant Professor
University of Louisville