High-grade Gliomas (HGG)Phase 2NCT07694089
Steroid Avoidance, Dexamethasone, and RAGE Inhibition for Perioperative Cerebral Edema Management in High-Grade Gliomas
A Phase 2 study testing Dexamethasone and Azeliragon in people with High-grade Gliomas (HGG), run by Akshitkumar MIstry at 2 sites in United States.
Trial summary
The purpose of this study is to learn whether two alternatives to standard steroid treatment can safely control swelling around a brain tumor after surgery. The study will compare three approaches by placing participants in one of three study groups: standard dexamethasone (a steroid), no routine steroid treatment… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- High-grade Gliomas (HGG)
- What is being tested?
- Dexamethasone and Azeliragon
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Oct 2026to 1 Aug 2029
- Phase
- Phase 2
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years at the time of screening
- Newly diagnosed supratentorial tumor with imaging characteristics consistent with high-grade glioma
- Candidate for craniotomy with planned resection of more than 50% of the contrast-enhancing tumor
- Midline shift ≤10 mm on preoperative imaging
- Limited pre-enrollment corticosteroid exposure (≤10 mg dexamethasone total and no chronic steroid use within 30 days)
- Karnofsky Performance Status ≥60
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- Adequate organ function to undergo surgery and postoperative care as determined by the investigator
- Ability to provide informed consent and comply with study procedures
- Agreement to use effective contraception, when applicable
Who cannot join
- Participants meeting any of the following will be excluded:
- Imaging or clinical features highly suggestive of primary CNS lymphoma or metastatic disease
- Posterior fossa tumors or lesions associated with high risk of brainstem compression
- Leptomeningeal or widely disseminated disease
- Clinical conditions requiring immediate corticosteroid therapy
- Prior exposure to high-dose corticosteroids (>10 mg dexamethasone) or chronic steroid use within 30 days
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- Active systemic illness that increases surgical risk, including uncontrolled infection, coagulopathy, or severe cardiopulmonary disease
- Pregnancy or breastfeeding
- Known immunodeficiency or chronic infection requiring immunosuppressive therapy
- Use of investigational agents within 30 days or concurrent use of immunosuppressive medications not permitted by protocol
- Known hypersensitivity to azeliragon
- Inability to undergo MRI due to contraindications such as incompatible implants or severe claustrophobia
- Life expectancy less than 3 months as determined by the investigator
- Participation in another interventional clinical trial prior to initiation of standard adjuvant therapy Vulnerable Populations: This study will not enroll children, pregnant or breastfeeding individuals, or prisoners. Individuals with impaired decision-making capacity may be enrolled only when a legally authorized representative is available to provide consent in accordance with institutional and regulatory requirements.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
UofL Health Brown Cancer Center contact
United States2 sites
UofL Health Brown Cancer Center; University of Louisville Hospital
Louisville, Kentucky, 40202
UofL Health Brown Cancer Center, 502-562-4370
UofL Health Jewish Hospital
Louisville, Kentucky, 40202
About this study
Official title: A Randomized Trial of Steroid Avoidance, Dexamethasone, and RAGE Inhibition for Perioperative Cerebral Edema Management in High-Grade Gliomas
The purpose of this study is to learn whether two alternatives to standard steroid treatment can safely control swelling around a brain tumor after surgery. The study will compare three approaches by placing participants in one of three study groups: standard dexamethasone (a steroid), no routine steroid treatment, and azeliragon, a study drug that may reduce brain swelling through a different pathway. Researchers want to determine whether these alternatives can control swelling while reducing some of the side effects associated with steroid use.
Participants in this study will be randomly assigned to one of three study groups. Participants will undergo their planned brain tumor surgery and receive the treatment assigned to their group. Study procedures are the same as their routine care and include physical and neurological examinations, blood tests, MRI scans, review of medical records, and collection of tumor tissue removed during surgery (optional). Most study visits will occur during routine medical care. Participants will be followed for approximately 24 months after surgery.
Read the detailed description
This study is a randomized Phase II trial because it is designed to evaluate the preliminary efficacy, safety, and feasibility of steroid avoidance and azeliragon as alternatives to dexamethasone for perioperative cerebral edema management in high-grade glioma. The trial uses an intermediate imaging-based efficacy endpoint, enrolls a modest sample size, and is intended to identify promising strategies for subsequent confirmation in a definitive Phase III study.
The trial compares three perioperative strategies-standard dexamethasone, complete steroid avoidance, and RAGE inhibition with azeliragon-to determine their relative safety and effectiveness in controlling cerebral edema following tumor resection. In addition to edema control, the study evaluates clinical, functional, and immunologic outcomes associated with perioperative corticosteroid exposure.
Despite widespread use, dexamethasone lacks prospective evidence defining its optimal perioperative role in glioma patients. This study addresses that gap by rigorously evaluating steroid avoidance and a mechanistically targeted alternative, with the goal of improving patient outcomes while minimizing treatment-related toxicity.
- Conditions
- High-grade Gliomas (HGG)
- Being tested
- Dexamethasone, Azeliragon
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Potent FDA-approved corticosteroid
AzeliragonDrug
orally bioavailable inhibitor of the receptor for advanced glycation endproducts (RAGE)
| Study group | Role | What they receive |
|---|---|---|
| Dexamethasone Arm | Active comparator | Standard dexamethasone (steroid) treatment Receives: Drug: Dexamethasone |
| No-dexamethasone Arm | No intervention | No routine dexamethasone treatment |
| Azeliragon Arm | Experimental | Azeliragon administered for the treatment of brain cancer and to evaluate its capability to control brain swelling around the time of surgery. Receives: Drug: Azeliragon |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in peritumoral edema between the preoperative and postoperative period
The primary outcome is the change in peritumoral edema between the preoperative and postoperative period. Specifically, it is the ratio of postoperative to preoperative peritumoral edema volume, adjusted for extent of enhancing tumor removed. This outcome is derived from MRI-based volumetric assessment and reflects the effectiveness of each perioperative strategy in controlling cerebral edema while accounting for surgical factors
Measured: before the start of adjuvant chemo radiation (up to 6 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2026
- Study start1 Oct 2026 (estimated)
- Primary completion1 Aug 2029 (estimated)
- Study completion1 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High-grade Gliomas (HGG)Studies of the same condition, open and under way.
- 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
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase II, single-center, randomized, open-label, three-arm parallel-group study
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Akshitkumar MIstry
- Sponsor type
- University, hospital or other
- Collaborators
- Cantex Pharmaceuticals Inc., James Graham Brown Cancer Center
- Responsible party
- Sponsor-investigator, Akshitkumar MIstry, University of Louisville
- Investigators
- Akshitkumar M Mistry, MD, Principal investigator, UofL Health - Brown Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07694089
- Sponsor's protocol ID
- ROID-RAGE-HGG
- Status last verified
- Jul 2026
- First submitted
- 30 Jun 2026
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: name, address, date of birth, medical history, and other information from your medical records from UofL Health and other institutions involved with this research, as well as from your other healthcare providers (which may include information about HIV status, drug, alcohol or sexually transmitted disease treatment, genetic test results, or mental health treatment)
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Steroid Avoidance, Dexamethasone, and RAGE Inhibition for Perioperative Cerebral Edema Management in High-Grade Gliomas
- ClinicalTrials.gov ID
- NCT07694089
- Acronym / sponsor ID
- ROID-RAGE-HGG
- Conditions
- High-grade Gliomas (HGG)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Akshitkumar MIstryUniversity, hospital or other
- Collaborators
- Cantex Pharmaceuticals Inc., James Graham Brown Cancer Center
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 1 Aug 2029 (estimated)
- Study completion
- 1 Aug 2029 (estimated)
- First posted
- 9 Jul 2026 (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.
The purpose of this study is to learn whether two alternatives to standard steroid treatment can safely control swelling around a brain tumor after surgery. The study will compare three approaches by placing participants in one of three study groups: standard dexamethasone (a steroid), no routine steroid treatment, and azeliragon, a study drug that may reduce brain swelling through a different pathway. Researchers want to determine whether these alternatives can control swelling while reducing some of the side effects associated with steroid use.
Participants in this study will be randomly assigned to one of three study groups. Participants will undergo their planned brain tumor surgery and receive the treatment assigned to their group. Study procedures are the same as their routine care and include physical and neurological examinations, blood tests, MRI scans, review of medical records, and collection of tumor tissue removed during surgery (optional). Most study visits will occur during routine medical care. Participants will be followed for approximately 24 months after surgery.
Detailed description
This study is a randomized Phase II trial because it is designed to evaluate the preliminary efficacy, safety, and feasibility of steroid avoidance and azeliragon as alternatives to dexamethasone for perioperative cerebral edema management in high-grade glioma. The trial uses an intermediate imaging-based efficacy endpoint, enrolls a modest sample size, and is intended to identify promising strategies for subsequent confirmation in a definitive Phase III study.
The trial compares three perioperative strategies-standard dexamethasone, complete steroid avoidance, and RAGE inhibition with azeliragon-to determine their relative safety and effectiveness in controlling cerebral edema following tumor resection. In addition to edema control, the study evaluates clinical, functional, and immunologic outcomes associated with perioperative corticosteroid exposure.
Despite widespread use, dexamethasone lacks prospective evidence defining its optimal perioperative role in glioma patients. This study addresses that gap by rigorously evaluating steroid avoidance and a mechanistically targeted alternative, with the goal of improving patient outcomes while minimizing treatment-related toxicity.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Phase II, single-center, randomized, open-label, three-arm parallel-group study
| Arm | Type | Receives |
|---|---|---|
| Dexamethasone Arm | Active comparator | Drug: DexamethasoneStandard dexamethasone (steroid) treatment |
| No-dexamethasone Arm | No intervention | –No routine dexamethasone treatment |
| Azeliragon Arm | Experimental | Drug: AzeliragonAzeliragon administered for the treatment of brain cancer and to evaluate its capability to control brain swelling around the time of surgery. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥18 years at the time of screening
- Newly diagnosed supratentorial tumor with imaging characteristics consistent with high-grade glioma
- Candidate for craniotomy with planned resection of more than 50% of the contrast-enhancing tumor
- Midline shift ≤10 mm on preoperative imaging
- Limited pre-enrollment corticosteroid exposure (≤10 mg dexamethasone total and no chronic steroid use within 30 days)
Key exclusion criteria (14 listed)
- Participants meeting any of the following will be excluded:
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 |
|---|---|---|
| DexamethasonePotent FDA-approved corticosteroid | Drug | Dexamethasone Arm |
| Azeliragonorally bioavailable inhibitor of the receptor for advanced glycation endproducts (RAGE) | Drug | Azeliragon Arm |
Primary outcome
change in peritumoral edema between the preoperative and postoperative period
Time frame: before the start of adjuvant chemo radiation (up to 6 weeks)
The primary outcome is the change in peritumoral edema between the preoperative and postoperative period. Specifically, it is the ratio of postoperative to preoperative peritumoral edema volume, adjusted for extent of enhancing tumor removed. This outcome is derived from MRI-based volumetric assessment and reflects the effectiveness of each perioperative strategy in controlling cerebral edema while accounting for surgical factors
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 9 Jul 2026.
- Individual participant dataSharing planned: Yes. name, address, date of birth, medical history, and other information from your medical records from UofL Health and other institutions involved with this research, as well as from your other healthcare providers (which may include information about HIV status, drug, alcohol or sexually transmitted disease treatment, genetic test results, or mental health treatment)
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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.
UofL Health Brown Cancer Center contact
Akshitkumar M Mistry, MD principal investigator
UofL Health - Brown Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dexamethasone and Azeliragon in people with High-grade Gliomas (HGG), run by Akshitkumar MIstry at 2 sites 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 9 inclusion and 14 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: opening soon, as of the sponsor's last update on 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Akshitkumar M Mistry, MD (502-276-5030, a.mistry@uoflhealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change in peritumoral edema between the preoperative and postoperative period (time frame: before the start of adjuvant chemo radiation (up to 6 weeks)). 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 9 Jul 2026.