GlioblastomaEarly Phase 1NCT06831526
Neoadjuvant Chemoradiotherapy With or Without Concurrent Azeliragon in Patients With Newly Diagnosed Glioblastoma
A Early Phase 1 study testing Azeliragon, Temozolomide and Radiation therapy in people with Glioblastoma, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Azeliragon, Temozolomide and Radiation therapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Nov 2025to 31 Aug 2030
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Jiayi Huang, M.D., 314-362-8567, jiayi.huang@wustl.edu
Jiayi Huang, M.D.
About this study
Official title: A Window-of-opportunity Early Phase I Randomized Study of Neoadjuvant Chemoradiotherapy With or Without Concurrent Azeliragon in Patients With Newly Diagnosed Glioblastoma
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
- Being tested
- Azeliragon, Temozolomide, Radiation therapy, Surgery or LITT
- Keywords
- GBM, Neoadjuvant chemoradiotherapy, Azeliragon, RAGE inhibitor, Window of opportunity study
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzeliragonDrug
Provided by Cantex Pharmaceuticals
TemozolomideDrug
Also called TMZ
Standard of care.
Radiation therapyRadiation
Standard of care.
Surgery or LITTProcedure or surgery
Standard of care surgical resection or laser interstitial thermal therapy (LITT).
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Neoadjuvant RT and Temozolomide (TMZ) + Surgery or LITT + Adjuvant TMZ & Azeliragon | Active comparator | 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. Receives: Drug: Azeliragon; Drug: Temozolomide; Radiation: Radiation therapy; Procedure: Surgery or LITT |
| Arm 2: Neoadjuvant RT, Temozolomide (TMZ) & Azeliragon + Surgery or LITT + Adjuvant TMZ & Azeliragon | Experimental | 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. Receives: Drug: Azeliragon; Drug: Temozolomide; Radiation: Radiation therapy; Procedure: Surgery or LITT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of immune-suppressive myeloid cells in the tumor tissue
Measured: At time of surgery or LITT (estimated to be day 60)
Percentage of immune-suppressive T cells in the tumor tissue
Measured: At time of surgery or LITT (estimated to be day 60)
Secondary outcomes (5)
Number of participants with adverse events
Measured: From day 1 (Arm 1) or Day -6 (Arm 2) through 30 days after last dose of azeliragon (estimated to be 10 months)
Number of participants with intolerable toxicities
The protocol lists the specific toxicities that are considered intolerable.
Measured: From first dose of azeliragon until 30 days after the last dose (estimated to be 6-9 months)
Progression-free survival (PFS)
Measured: Up to 12 months after completion of study treatment (estimated to be 21 months)
Overall survival (OS)
Measured: Up to 12 months after completion of study treatment (estimated to be 21 months)
Feasibility of the regimen as measured by the number of participants who proceed with post-chemoradiotherapy surgery or LITT
Feasibility is defined as at least 50% of patients in each arm who are able to proceed with post-chemoradiotherapy surgery or LITT.
Measured: Through surgery or LITT (estimated to be 60 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2025
- Study start6 Nov 2025
- Primary completion28 Feb 2029 (estimated)
- Study completion31 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Cantex Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Jiayi Huang, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06831526
- Sponsor's protocol ID
- 202504190
- Status last verified
- May 2026
- First submitted
- 12 Feb 2025
- Last updated
- 29 May 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Window-of-opportunity Early Phase I Randomized Study of Neoadjuvant Chemoradiotherapy With or Without Concurrent Azeliragon in Patients With Newly Diagnosed Glioblastoma
- ClinicalTrials.gov ID
- NCT06831526
- Acronym / sponsor ID
- 202504190
- Conditions
- Glioblastoma
- Keywords
- GBM, Neoadjuvant chemoradiotherapy, Azeliragon, RAGE inhibitor, Window of opportunity study
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Cantex Pharmaceuticals
- Study start
- 6 Nov 2025 (actual)
- Primary completion
- 28 Feb 2029 (estimated)
- Study completion
- 31 Aug 2030 (estimated)
- First posted
- 18 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Neoadjuvant RT and Temozolomide (TMZ) + Surgery or LITT + Adjuvant TMZ & Azeliragon | Active comparator | Drug: Azeliragon, Drug: Temozolomide, Radiation: Radiation therapy, Procedure: Surgery or LITTRadiation 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. |
| Arm 2: Neoadjuvant RT, Temozolomide (TMZ) & Azeliragon + Surgery or LITT + Adjuvant TMZ & Azeliragon | Experimental | Drug: Azeliragon, Drug: Temozolomide, Radiation: Radiation therapy, Procedure: Surgery or LITTRT 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzeliragonProvided by Cantex Pharmaceuticals | Drug | Arm 1: Neoadjuvant RT and Temozolomide (TMZ) + Surgery or LITT + Adjuvant TMZ & Azeliragon, Arm 2: Neoadjuvant RT, Temozolomide (TMZ) & Azeliragon + Surgery or LITT + Adjuvant TMZ & Azeliragon |
| TemozolomideAlso: TMZStandard of care. | Drug | Arm 1: Neoadjuvant RT and Temozolomide (TMZ) + Surgery or LITT + Adjuvant TMZ & Azeliragon, Arm 2: Neoadjuvant RT, Temozolomide (TMZ) & Azeliragon + Surgery or LITT + Adjuvant TMZ & Azeliragon |
| Radiation therapyStandard of care. | Radiation | Arm 1: Neoadjuvant RT and Temozolomide (TMZ) + Surgery or LITT + Adjuvant TMZ & Azeliragon, Arm 2: Neoadjuvant RT, Temozolomide (TMZ) & Azeliragon + Surgery or LITT + Adjuvant TMZ & Azeliragon |
| Surgery or LITTStandard of care surgical resection or laser interstitial thermal therapy (LITT). | Procedure or surgery | Arm 1: Neoadjuvant RT and Temozolomide (TMZ) + Surgery or LITT + Adjuvant TMZ & Azeliragon, Arm 2: Neoadjuvant RT, Temozolomide (TMZ) & Azeliragon + Surgery or LITT + Adjuvant TMZ & Azeliragon |
Primary outcome
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)
5 secondary outcomes
Number of participants with adverse events
Time frame: From day 1 (Arm 1) or Day -6 (Arm 2) through 30 days after last dose of azeliragon (estimated to be 10 months)
Number of participants with intolerable toxicities
Time frame: From first dose of azeliragon until 30 days after the last dose (estimated to be 6-9 months)
Progression-free survival (PFS)
Time frame: Up to 12 months after completion of study treatment (estimated to be 21 months)
Overall survival (OS)
Time frame: Up to 12 months after completion of study treatment (estimated to be 21 months)
Feasibility of the regimen as measured by the number of participants who proceed with post-chemoradiotherapy surgery or LITT
Time frame: Through surgery or LITT (estimated to be 60 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2026.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jiayi Huang, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Azeliragon, Temozolomide and Radiation therapy in people with Glioblastoma, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jiayi Huang, M.D. (314-362-8567, jiayi.huang@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2026.