High-grade Gliomas (HGG)
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGDexamethasone
Potent FDA-approved corticosteroid
DRUGAzeliragon
orally bioavailable inhibitor of the receptor for advanced glycation endproducts (RAGE)
Sponsors
Akshitkumar MIstry
Cantex Pharmaceuticals Inc.
James Graham Brown Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
Phase II, single-center, randomized, open-label, three-arm parallel-group study
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| change in peritumoral edema between the preoperative and postoperative period | 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 |
Countries
United States
Contacts
CONTACTAkshitkumar M Mistry, MD
CONTACTUofL Health Brown Cancer Center
PRINCIPAL_INVESTIGATORAkshitkumar M Mistry, MD
UofL Health - Brown Cancer Center
Outcome results
None listed