Neoadjuvant Chemoradiotherapy With or Without Concurrent Azeliragon in Patients With Newly Diagnosed Glioblastoma

Conditions

• Glioblastoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Azeliragon — DRUG
  Provided by Cantex Pharmaceuticals
• Temozolomide — DRUG
  Standard of care.
• Radiation therapy — RADIATION
  Standard of care.
• Surgery or LITT — PROCEDURE
  Standard of care surgical resection or laser interstitial thermal therapy (LITT).

Study Details

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.

Key Dates

Start date

Nov 6, 2025

Status verified

May 2026

Primary completion

Feb 28, 2029

Completion

Aug 31, 2030

Study Design

Enrollment

12 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

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.

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) ]

Central Contacts

• Jiayi Huang, M.D.
  314-362-8567
  [email protected]

Locations (1)

Find similar trials in St Louis, MO

Related Studies

• SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry
  Recruiting · Massive Bio, Inc. · Birmingham, Alabama
• A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma
  PHASE2/PHASE3 · Recruiting · Global Coalition for Adaptive Research · Birmingham, Alabama
• Immunotherapy Before and After Surgery for Treatment of Recurrent or Progressive High Grade Glioma in Children and Young Adults
  PHASE1 · Recruiting · Sabine Mueller, MD, PhD · Birmingham, Alabama
• Sonobiopsy for Noninvasive and Sensitive Detection of Glioblastoma
  Recruiting · Washington University School of Medicine · St Louis, Missouri