NCT05773664

Dexamethasone and Azeliragon for Management of Post-Resection Cerebral Edema in Patients with Glioblastoma

A Phase I De-Escalation Study of Dexamethasone with Azeliragon for Management of Post-Resection Cerebral Edema in Patients with Glioblastoma

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of dexamethasone when given with azeliragon in managing cerebral edema after surgery (post-resection) in patients with glioblastoma. Cerebral edema is a pathological increase in the water mass contained within the brain interstitial space. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Azeliragon is an oral RAGE inhibitor. Blocking the RAGE pathway at the time of surgery (peri-operatively) may decrease cerebral edema. Giving dexamethasone with azeliragon may help control post-operative cerebral edema in decreasing doses of concurrently administered dexamethasone.

Detailed description

PRIMARY OBJECTIVES: I. Determine the lowest dose of dexamethasone that needs to be co-administered with azeliragon for treatment of post-resection cerebral edema in patients with glioblastoma. II. Assess the safety of administering azeliragon peri-operatively to patients with glioblastoma. SECONDARY OBJECTIVES: I. Describe post-operative changes in levels of cytokines and chemokines in brain interstitium and peripheral blood in study participants. II. Quantitatively assess changes in the volume of cerebral edema post-operatively in study participants. III. Determine brain concentrations of azeliragon in resected tumor tissue from Arm 1 participants. EXPLORATORY OBJECTIVES: I. Describe post-operative changes in levels of RAGE ligands in brain interstitium, peripheral blood, and resection cavity fluid (when possible to obtain) in study participants. II. Describe changes in levels of cytokines, chemokines, and immune cell populations in resection cavity fluid (when possible to obtain). III. Describe differences in levels of cytokines, chemokines and RAGE ligands between patients in Arm 1 and Arm 2. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive azeliragon orally (PO) and dexamethasone PO or intravenously (IV) throughout the study. Patients also undergo collection of cavity fluid and blood samples, computed tomography (CT) scan, and brain magnetic resonance imaging (MRI) with or without contrast throughout the study. ARM II: Patients receive dexamethasone PO or IV throughout the study. Patients also undergo collection of cavity fluid and blood samples, CT scan, and brain MRI with or without contrast throughout the study.

Conditions

• Glioblastoma
• Malignant Glioma

Interventions

Type	Name	Description
DRUG	Azeliragon	Given PO
PROCEDURE	Biospecimen Collection	Undergo collection of cavity fluid and blood samples
PROCEDURE	Computed Tomography	Undergo CT scan
DRUG	Dexamethasone	Given PO or IV
PROCEDURE	Magnetic Resonance Imaging of the Brain with and without Contrast	Undergo MRI with or without contrast

Timeline

• Start date: 2024-11-15
• Primary completion: 2024-11-29
• Completion: 2024-11-29
• First posted: 2023-03-17
• Last updated: 2024-09-19

Regulatory

• FDA-regulated drug study