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

NCT05773664 | Withdrawn Phase 1 DMC FDA Drug

• 4 other identifiers: 22367NCI-2023-00007P30CA033572U19CA264512
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Glioblastoma; Malignant Glioma

Outcome Measures

Primary Outcomes (2)

• Lack of feasibility

  Defined by exceeding the planned total dose of dexamethasone (per dose level) during post-operative days 1 to 8 by approximately 50%.

  Up to 8 days after surgery

• Incidence of adverse events

  Azeliragon related adverse events and dose limiting toxicity rate assessed per Common Terminology Criteria for Adverse Events version 5.0.

  Up to 30 days post-last dose of protocol therapy

Secondary Outcomes (3)

• Cytokines/chemokines

  Up to 3 days after surgery

• Volume of cerebral edema

  Up to 8 days after surgery

• Azeliragon concentrations

  Up to 8 days after surgery

Study Arms (2)

Arm I (azeliragon, dexamethasone)

EXPERIMENTAL

Patients receive azeliragon PO and 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.

Drug: Azeliragon; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Dexamethasone; Procedure: Magnetic Resonance Imaging of the Brain with and without Contrast

Arm II (dexamethasone)

ACTIVE COMPARATOR

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.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Dexamethasone; Procedure: Magnetic Resonance Imaging of the Brain with and without Contrast

Interventions

Azeliragon DRUG

Given PO

Arm I (azeliragon, dexamethasone)

Biospecimen Collection PROCEDURE

Undergo collection of cavity fluid and blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (azeliragon, dexamethasone); Arm II (dexamethasone)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Arm I (azeliragon, dexamethasone); Arm II (dexamethasone)

Dexamethasone DRUG

Given PO or IV

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Arm I (azeliragon, dexamethasone); Arm II (dexamethasone)

Magnetic Resonance Imaging of the Brain with and without Contrast PROCEDURE

Undergo MRI with or without contrast

Also known as: Brain Magnetic Resonance Imaging with and without Contrast, Brain MRI, Brain MRI with and without Contrast, Head MRI with and without Contrast

Arm I (azeliragon, dexamethasone); Arm II (dexamethasone)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Age: \>= 18 years
• Karnofsky performance status of \>= 60%
• Histologically confirmed glioblastoma or radiographic findings consistent with a high grade glioma in patients undergoing surgery for initial diagnosis
• If midline shift is present on the pre-op brain MRI, it must be less than 10 mm
• The patient is planning to undergo a standard of care craniotomy, and the neurosurgeon anticipates being able to perform a gross total resection of tumor
• If a patient is taking more than 3 mg twice daily (bid) of dexamethasone at the time of signing the consent form, it is anticipated by the neurosurgeon that the participant will be able to decrease their dose of dexamethasone to 3 mg bid by 6 days before the surgery
• Note: If the patient is not able to decrease their dose of dexamethasone to 3 mg BID 6 days before surgery, then the patient will not be allowed to participate in the study
• The patient is not planning to participate in another clinical trial during the study period
• The patient has recovered from any acute toxic effects (except alopecia) to =\< grade 1 of prior anti-cancer therapy
• Absolute neutrophil count (ANC) \>= 1,000/mm\^3
• Platelets \>= 100,000/mm\^3
• Total bilirubin =\< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease)
• Aspartate aminotransferase (AST) =\< 1.5 x ULN
• Alanine aminotransferase (ALT) =\< 1.5 x ULN

You may not qualify if:

• Less than 6 weeks since taking a nitrosourea-containing chemotherapy regimen; less than 4 weeks since completing a non-nitrosourea-containing cytotoxic chemotherapy regimen (except temozolomide: only patients with an interval of less than 23 days from the last dose administered when treated with the temozolomide regimen of daily for 5 days, repeated every 28 days are excluded); less than 2 weeks from taking the last dose of a targeted agent; less than 4 weeks from the last dose of bevacizumab
• Less than 3 months since focal brain radiation unless recurrent disease has been confirmed surgically or the area of recurrent tumor is outside of the radiation field
• The patient is taking a medication that is a strong CYP3A4 inducers/ inhibitors within 14 days prior to day -6 of protocol therapy
• The patient is unwilling to stop taking herbal medications prior to the start of study treatment
• The patient is taking a hepatic enzyme-inducing anticonvulsant within 14 days prior to day -6 of protocol therapy
• Clinically significant uncontrolled illness
• Active infection requiring antibiotics
• Human immunodeficiency virus (HIV)-positive
• Undergoing treatment for another cancer
• Issues with tolerating oral medication (e.g. inability to swallow pills, malabsorption issues, ongoing nausea or vomiting)
• Chronic or active viral infection of the central nervous system (CNS)
• Pregnant or breastfeeding
• Coagulopathy or bleeding disorder
• Inability to undergo a brain MRI
• Inability to tolerate dexamethasone

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

azeliragon; Specimen Handling; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Contrast Media

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Diagnostic Uses of Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Study Officials

• Jana L Portnow

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: March 17, 2023
• Study Start: November 15, 2024
• Primary Completion: November 29, 2024
• Study Completion: November 29, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09