Recruiting
Early Phase 1

Azeliragon, RT & TMZ

Sponsor:

Washington University School of Medicine

Code:

NCT06831526

Conditions

Glioblastoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Azeliragon

Temozolomide

Radiation therapy

Surgery or LITT

Study Details

Brief summary:

Preclinical data have demonstrated the combination of azeliragon, a RAGE inhibitor, with radiation therapy (RT) can effectively reduce immune-suppressive myeloid cells and restore T-cell activation to improve tumor control in murine glioma models. Ongoing clinical studies of azeliragon with RT alone and RT plus temozolomide (TMZ) to treat patients with newly diagnosed glioblastoma (GBM) have demonstrated safety and tolerability. The purpose of this window-of-opportunity study is to validate that the combination of azeliragon with RT and TMZ would modulate immune-suppressive myeloid and T cells in the tumor microenvironment in patients with GBM.

Conditions

Glioblastoma

Study ID

NCT06831526

Start date

Nov 6, 2025

Status verified date

May, 2026

Completion date

Aug 31, 2030

Anticipated

Primary completion date

Feb 28, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Histologically proven diagnosis of IDH-wildtype GBM (WHO grade 4) according to the 2021 WHO classification (including subtypes such as gliosarcoma).
  • Radiographic evidence of residual tumor after initial surgery or biopsy.
  • Patient is amenable for future surgery (either surgical resection or laser interstitial thermal therapy (LITT)) to sample the residual tumor after completion of chemoradiotherapy.
  • At least 18 years of age.
  • Eligible for and planning to receive standard fractionated RT of 60 Gy with concurrent TMZ.
  • Recovered from the effects of surgery, postoperative infection, and other complications sufficiently for initiation of chemoradiotherapy, in the opinion of the treating physician.
  • Karnofsky performance status ≥ 60.
  • Adequate organ and bone marrow function as defined below:

  • Absolute neutrophil count (ANC) ≥ 1.5 K/cumm;
  • Platelets ≥ 100 K/cumm;
  • Hemoglobin > 9.0 g/dL (Note: the use of transfusion or other intervention to achieve Hgb >9.0 g/dL is acceptable);
  • Total bilirubin ≤ 1.5 ULN
  • AST (SGOT) and ALT (SGPT) ≤ 3 x ULN
  • Creatinine ≤ 1.5 ULN or creatinine clearance ≥ 60 mL/min
  • If there is history of human immunodeficiency virus (HIV) infection, patients must be on effective antiretroviral therapy, and HIV viral load must be undetectable within 6 months of study enrollment.
  • If there is history of chronic hepatitis B virus (HBV) infection, patients must have either been treated or are on suppressive therapy (as indicated), and HBV viral load must be undetectable.
  • If there is history of hepatitis C virus (HCV) infection, patients must have been treated, and HCV viral load must be undetectable.
  • Females of childbearing potential (defined as a female who is non-menopausal or surgically sterilized) and sexually active heterosexual males must be willing to use an acceptable method of birth control (i.e., hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the trial and for 6 months after the last administration of azeliragon. Should a female trial participant or female partner of a male trial participants become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Able to understand and willingness to sign an IRB-approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

  • Prior cranial RT or RT to the head and neck where potential field overlap may exist.
  • Leptomeningeal or metastatic involvement.
  • Known IDH mutation. IDH status could be determined by either immunohistochemistry or sequencing as evaluated per routine clinical care.
  • Patients receiving CYP 2C8 inhibitors within 2 weeks or 5 half-lives prior to study entry.
  • Patients with a gastrointestinal condition that could interfere with swallowing or absorption.
  • Patients with concurrent participation in another interventional clinical trial or use of another investigational agent within 30 days prior to study entry. Patients who are participating in non-interventional clinical trials (e.g., QOL, imaging, observational, follow-up studies, etc.) are eligible, regardless of the timing of participation.
  • Medical contraindication to MRI (e.g., unsafe foreign metallic implants, incompatible pacemaker, inability to lie still for long periods, severe to end-stage kidney disease or on hemodialysis).
  • Pregnant or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of the first dose of RT (Arm 1) or azeliragon (Arm 2).
  • Patients with psychiatric illness/social situations, including alcohol or drug abuse that in the investigator's opinion will prevent administration or completion of protocol therapy.
  • Non-English speaking, as the cognitive assessments will only be available in English

Study Design

Enrollment

12 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Arm 1: Neoadjuvant RT and Temozolomide (TMZ) + Surgery or LITT + Adjuvant TMZ & Azeliragon

Radiation therapy (RT) will consist of fractionated RT to 60 Gy in 30 daily fractions administered per standard of care RTOG approach. Concurrent TMZ during RT will be self-administered by mouth (PO) as per standard of care. 1 month after completion of RT, patient will proceed with planned surgery of either resection or LITT. Patients will then receive adjuvant TMZ and azeliragon for up to 6 months. Patient should start with the loading dose 30 mg BID for 6 days before the start of adjuvant TMZ. After 6 days, azeliragon 20 mg once daily should be continued in combination with TMZ.

experimental: Arm 2: Neoadjuvant RT, Temozolomide (TMZ) & Azeliragon + Surgery or LITT + Adjuvant TMZ & Azeliragon

RT will consist of fractionated RT to 60 Gy in 30 daily fractions administered per standard of care RTOG approach. Concurrent TMZ during RT will be self-administered by mouth (PO) as per standard of care. Patients will receive azeliragon as well. Azeliragon is self-administered PO. Azeliragon dosing will consist of 6 days of a loading dose of 30 mg twice per day starting on day -6, followed by 20 mg daily starting on the Day 1. Concurrent RT and TMZ start on Day 1. Azeliragon should continue until the day before planned surgical procedure. 1 month after completion of RT, patient will proceed with planned surgery of either resection or LITT. Patients will then receive adjuvant TMZ and azeliragon for up to 6 months. Patient should start with the loading dose 30 mg BID for 6 days before the start of adjuvant TMZ. After 6 days, azeliragon 20 mg once daily should be continued in combination with TMZ.

Interventions

Azeliragon

Provided by Cantex Pharmaceuticals

Temozolomide

Standard of care.

Radiation therapy

Standard of care.

Surgery or LITT

Standard of care surgical resection or laser interstitial thermal therapy (LITT).

Primary outcome measure

  • Percentage of immune-suppressive myeloid cells in the tumor tissue [ Time Frame: At time of surgery or LITT (estimated to be day 60) ]
  • Percentage of immune-suppressive T cells in the tumor tissue [ Time Frame: At time of surgery or LITT (estimated to be day 60) ]

Central Contacts and Locations

Central contacts

Jiayi Huang, M.D.

314-362-8567jiayi.huang@wustl.edu

Locations

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Jiayi Huang, M.D.

314-362-8567jiayi.huang@wustl.edu

Principal Investigator:

Jiayi Huang, M.D.

More Information

Sponsor

Washington University School of Medicine

Last update posted

May 29, 2026

Last verified

May, 2026

Keywords

  • GBM
  • Neoadjuvant chemoradiotherapy
  • Azeliragon
  • RAGE inhibitor
  • Window of opportunity study

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Washington University School of Medicine on 2026-05-29.