Steroid Avoidance, Dexamethasone, and RAGE Inhibition for Perioperative Cerebral Edema Management in High-Grade Gliomas

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

Exclusion Criteria:

• 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.