GlioblastomaPhase 1NCT05773664
Dexamethasone and Azeliragon for Management of Post-Resection Cerebral Edema in Patients with Glioblastoma
A Phase 1 study testing Azeliragon, Biospecimen Collection and Computed Tomography in people with Glioblastoma and Malignant Glioma, run by City of Hope Medical Center.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Malignant Glioma
- What is being tested?
- Azeliragon, Biospecimen Collection and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 15 Nov 2024to 29 Nov 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- 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
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- 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
- Creatinine clearance of >= 60 mL/min by the Cockcroft-Gault formula
- International normalized ratio (INR) OR prothrombin (PT) =< 1.5 x ULN
- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN
- Corrected QT (QTc) =< 480 ms
- Note: To be performed within 28 days prior to day 1 of protocol therapy
- People of childbearing potential: negative urine or serum pregnancy test
- Agreement by people of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
- Childbearing potential defined as not being surgically sterilized (regardless of gender) or not being free from menses for > 1 year (people with uteri only)
Who cannot join
- 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
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- 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
- Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
About this study
Official title: A Phase I De-Escalation Study of Dexamethasone with Azeliragon for Management of Post-Resection Cerebral Edema in Patients with Glioblastoma
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.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the lowest dose of dexamethasone that needs to be co-administered with azeliragon for treatment of post-resection cerebral edema in patients with glioblastoma.
II. Assess the safety of administering azeliragon peri-operatively to patients with glioblastoma.
SECONDARY OBJECTIVES:
- Describe post-operative changes in levels of cytokines and chemokines in brain interstitium and peripheral blood in study participants.
II. Quantitatively assess changes in the volume of cerebral edema post-operatively in study participants.
III. Determine brain concentrations of azeliragon in resected tumor tissue from Arm 1 participants.
EXPLORATORY OBJECTIVES:
- Describe post-operative changes in levels of RAGE ligands in brain interstitium, peripheral blood, and resection cavity fluid (when possible to obtain) in study participants.
II. Describe changes in levels of cytokines, chemokines, and immune cell populations in resection cavity fluid (when possible to obtain).
III. Describe differences in levels of cytokines, chemokines and RAGE ligands between patients in Arm 1 and Arm 2.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive azeliragon orally (PO) and dexamethasone PO or intravenously (IV) throughout the study. Patients also undergo collection of cavity fluid and blood samples, computed tomography (CT) scan, and brain magnetic resonance imaging (MRI) with or without contrast throughout the study.
ARM II: 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.
- Conditions
- Glioblastoma, Malignant Glioma
- Being tested
- Azeliragon, Biospecimen Collection, Computed Tomography, Dexamethasone, Magnetic Resonance Imaging of the Brain with and without Contrast
- Medical subject headings
- Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzeliragonDrug
Given PO
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo collection of cavity fluid and blood samples
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT scan
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO or IV
Magnetic Resonance Imaging of the Brain with and without ContrastProcedure or surgery
Also called Brain Magnetic Resonance Imaging with and without Contrast, Brain MRI, Brain MRI with and without Contrast, Head MRI with and without Contrast
Undergo MRI with or without contrast
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Dexamethasone; Procedure: Magnetic Resonance Imaging of the Brain with and without Contrast |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%.
Measured: 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.
Measured: Up to 30 days post-last dose of protocol therapy
Secondary outcomes (3)
Cytokines/chemokines
Will assess cytokines/chemokines in brain interstitium and peripheral blood. The cytokine and chemokine levels will be measured as concentrations (pg/mL) and reported as a median with range.
Measured: Up to 3 days after surgery
Volume of cerebral edema
Will assess volume of cerebral edema for each post-surgery brain magnetic resonance imaging (MRI) as measured qualitatively and quantitatively by manual segmentation and computer assisted techniques.
Measured: Up to 8 days after surgery
Azeliragon concentrations
Will assess azeliragon concentrations in tumor samples compared to azeliragon concentrations in blood.
Measured: Up to 8 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2023
- Study start15 Nov 2024 (estimated)
- Primary completion29 Nov 2024 (estimated)
- Study completion29 Nov 2024 (estimated)
Why it stopped: Funding
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 City of Hope Medical CenterThe 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jana L Portnow, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05773664
- Sponsor's protocol ID
- 22367
- Other IDs
- NCI-2023-00007, 22367, P30CA033572, U19CA264512
- Status last verified
- Sep 2024
- First submitted
- 30 Jan 2023
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I De-Escalation Study of Dexamethasone with Azeliragon for Management of Post-Resection Cerebral Edema in Patients with Glioblastoma
- ClinicalTrials.gov ID
- NCT05773664
- Acronym / sponsor ID
- 22367
- Conditions
- Glioblastoma, Malignant Glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 15 Nov 2024 (estimated)
- Primary completion
- 29 Nov 2024 (estimated)
- Study completion
- 29 Nov 2024 (estimated)
- First posted
- 17 Mar 2023 (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.
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.
Detailed description
PRIMARY OBJECTIVES:
- Determine the lowest dose of dexamethasone that needs to be co-administered with azeliragon for treatment of post-resection cerebral edema in patients with glioblastoma.
II. Assess the safety of administering azeliragon peri-operatively to patients with glioblastoma.
SECONDARY OBJECTIVES:
- Describe post-operative changes in levels of cytokines and chemokines in brain interstitium and peripheral blood in study participants.
II. Quantitatively assess changes in the volume of cerebral edema post-operatively in study participants.
III. Determine brain concentrations of azeliragon in resected tumor tissue from Arm 1 participants.
EXPLORATORY OBJECTIVES:
- Describe post-operative changes in levels of RAGE ligands in brain interstitium, peripheral blood, and resection cavity fluid (when possible to obtain) in study participants.
II. Describe changes in levels of cytokines, chemokines, and immune cell populations in resection cavity fluid (when possible to obtain).
III. Describe differences in levels of cytokines, chemokines and RAGE ligands between patients in Arm 1 and Arm 2.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive azeliragon orally (PO) and dexamethasone PO or intravenously (IV) throughout the study. Patients also undergo collection of cavity fluid and blood samples, computed tomography (CT) scan, and brain magnetic resonance imaging (MRI) with or without contrast throughout the study.
ARM II: 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (azeliragon, dexamethasone) | Experimental | Drug: Azeliragon, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Drug: Dexamethasone, Procedure: Magnetic Resonance Imaging of the Brain with and without ContrastPatients 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. |
| Arm II (dexamethasone) | Active comparator | Procedure: Biospecimen Collection, Procedure: Computed Tomography, Drug: Dexamethasone, Procedure: Magnetic Resonance Imaging of the Brain with and without ContrastPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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
Key exclusion criteria (17 listed)
- 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
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 |
|---|---|---|
| AzeliragonGiven PO | Drug | Arm I (azeliragon, dexamethasone) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionUndergo collection of cavity fluid and blood samples | Procedure or surgery | Arm I (azeliragon, dexamethasone), Arm II (dexamethasone) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT scan | Procedure or surgery | Arm I (azeliragon, dexamethasone), Arm II (dexamethasone) |
| DexamethasoneAlso: Aacidexam, Adexone, Aknichthol Dexa, Alba-DexGiven PO or IV | Drug | Arm I (azeliragon, dexamethasone), Arm II (dexamethasone) |
| Magnetic Resonance Imaging of the Brain with and without ContrastAlso: Brain Magnetic Resonance Imaging with and without Contrast, Brain MRI, Brain MRI with and without Contrast, Head MRI with and without ContrastUndergo MRI with or without contrast | Procedure or surgery | Arm I (azeliragon, dexamethasone), Arm II (dexamethasone) |
Primary outcome
Lack of feasibility
Time frame: Up to 8 days after surgery
Defined by exceeding the planned total dose of dexamethasone (per dose level) during post-operative days 1 to 8 by approximately 50%.
Incidence of adverse events
Time frame: Up to 30 days post-last dose of protocol therapy
Azeliragon related adverse events and dose limiting toxicity rate assessed per Common Terminology Criteria for Adverse Events version 5.0.
3 secondary outcomes
Cytokines/chemokines
Time frame: Up to 3 days after surgery
Volume of cerebral edema
Time frame: Up to 8 days after surgery
Azeliragon concentrations
Time frame: Up to 8 days after surgery
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
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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. This study is not recruiting at the moment.
Jana L Portnow principal investigator
City of Hope Medical Center
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Azeliragon, Biospecimen Collection and Computed Tomography in people with Glioblastoma and Malignant Glioma, run by City of Hope Medical Center.
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 23 inclusion and 17 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: withdrawn, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lack of feasibility (time frame: Up to 8 days after surgery). 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 19 Sep 2024.