High Grade GliomaPhase 1/2NCT07859059
Metronomic Temozolomide With Dexbrompheniramine for Recurrent High-Grade Glioma/Glioblastoma
A Phase 1/2 study testing Dexbrompheniramine and Temozolomide in people with High Grade Glioma and Glioblastoma, run by University of Nebraska at 1 site in United States.
Trial summary
The goal of this clinical trial is to: 1) evaluate the safety, tolerability, and recommended dose of dexbrompheniramine when combined with metronomic temozolomide for adults with recurrent high-grade glioma who have been previously treated with standard of care chemoradiation therapy and 2) determine the efficacy of… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- High Grade Glioma, Glioblastoma, Gliosarcoma
- What is being tested?
- Dexbrompheniramine and Temozolomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2027to 1 Jun 2031
- Phase
- Phase 1/2
- 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
- Pathologically proven diagnosis of high grade (aka grade 3 or 4) glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, glioblastoma, gliosarcoma).
- Patients must have received prior radiation therapy and standard temozolomide. Patients who have received any number of additional therapies for previous progressions will be considered eligible. Use of concurrent Optune is allowed.
- 1. Proven glioblastoma/gliosarcoma (2021 WHO criteria) that progressed after standard chemoradiation within the first six cycles of adjuvant TMZ.
- Must be three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression.
- Age ≥ 19 years of age
- Recovery from toxicity of any prior therapy that in the opinion of the investigator could impact tolerance to the study drug.
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- Adequate performance status: ECOG ≤ 2
- Adequate organ function:
- bone marrow reserve: (ANC ≥ 1,500 mm3, hemoglobin ≥ 8 g/dL, platelet count ≥ 100,000 mm3
- renal function: (serum creatinine ≤ 2.0 mg/dL)
- hepatic function: serum AST and ALT < 1.5 ULN, serum alkaline phosphatase < 2.5 ULN)
- Women of reproductive potential must be non-pregnant and non-nursing. (non child bearing potential is defined as age 55 years or older and no menses for two years or any age with surgical removal of the uterus and/or both ovaries) A negative pregnancy test is required within 7 days of initiating the study
- Both men and women must agree to employ an effective barrier method of birth control throughout the study and for either 3 months (males) or 6 months (females) after the last treatment dose.
- Patients must willingly provide written, informed consent after being informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts.
Who cannot join
- Any significant illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of oral dexbrompheniramine, or put the study outcomes at undue risk.
- Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
- Immunotherapy, chemotherapy, radiotherapy, corticosteroids (at dosages equivalent to prednisone > 20 mg/day) or experimental therapy within 4 weeks before the first dose of study drug
- Any other active malignancy other than nonmelanoma skin cancer or controlled prostate cancer
- Lactating or pregnant
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- Known history of intolerance to antihistamines due to glaucoma or urinary retention
- Ongoing treatment with MAO inhibitors. If MOAI medications can be safely stopped, a washout period of at least 2 weeks is required prior to starting dexbrompheniramine
- Planned concomitant use of CNS depressants, including alcohol, that represent a risk to subject safety or study outcomes per the determination of the principal investigator.
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
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Michaela K Savine, RN, 1(402)836-9488, misavine@unmc.edu
About this study
Official title: A Phase I/II Study of Metronomic Temozolomide With Dexbrompheniramine for Patients With Recurrent High-Grade Glioma/Glioblastoma
The goal of this clinical trial is to: 1) evaluate the safety, tolerability, and recommended dose of dexbrompheniramine when combined with metronomic temozolomide for adults with recurrent high-grade glioma who have been previously treated with standard of care chemoradiation therapy and 2) determine the efficacy of the combination therapy in adults with glioblastoma who progressed during the first six cycles of adjuvant standard dose temozolomide.
The main questions it aims to answer are:
Read more
- What medical problems to participants have when taking dexbrompheniramine together with temozolomide?
- What is the correct dose of dexbrompheniramine to use when evaluating the safety and efficacy of the combination therapy?
- Is the combination therapy more effective at delaying disease progression compared to temozolomide alone?
Participants will take dexbrompheniramine and temozolomide every day at night.
- Conditions
- High Grade Glioma, Glioblastoma, Gliosarcoma
- Being tested
- Dexbrompheniramine, Temozolomide
- Keywords
- Recurrent
- Medical subject headings
- Glioma, Glioblastoma, Gliosarcoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexbrompheniramineDrug
Also called ALA-HIST-IR
Antihistamine, HRH1 antagonist
TemozolomideDrug
Also called Temodar
DNA Alkylating Agent
| Study group | Role | What they receive |
|---|---|---|
| Arm I: Dose Finding | Experimental | Participants receive daily dexbrompheniramine (either 4 mg, 6 mg, or 8 mg) together with 50mg/m2/day temozolomide for up to one year or until progression or intolerance. Receives: Drug: Dexbrompheniramine; Drug: Temozolomide |
| Arm II: Treatment | Experimental | Participants receive daily dexbrompheniramine at the recommended phase 2 dose together with 50mg/m2/day temozolomide for up to one year or until progression or intolerance. Receives: Drug: Dexbrompheniramine; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and RP2D of Combination Therapy
Evaluate toxicity and determine the recommended dose of dexbrompheniramine with metronomic temozolomide in subjects with recurrent grade 3 and grade 4 glioma.
Measured: 24 months
Efficacy (PFS) of Combination Therapy
Evaluate efficacy (PFS) of the recommended dose of dexbrompheniramine with metronomic temozolomide in subjects with glioblastoma/gliosarcoma who progress during their first six cycles of adjuvant standard dose temozolomide. (Phase II)
Measured: 48 months
Secondary outcomes (10)
To measure blood concentration of dexbrompheniramine with temozolomide
Characterize pharmacokinetics (PK) of dexbrompheniramine with temozolomide in combination (Phase I) Population PK analyses will be used to estimate PK parameters for subjects with available PK sample collection, as means, SDs, medians, minimums, and maximums.
Measured: 24 months
Efficacy (PFS, OS, TTF)
Estimate progression free survival at 6 and 12 months, overall survival, and time to treatment failure (Both Phases).
Measured: 48 months
Examine quality of life changes using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30.)
Examine Quality of Life (QOL) using EORTC QLQ-C30 (Both Phases). EORTC QLQ-C30 will be summarized descriptively at each time point measured with mean, SD, median, and ranges in the intent-to-treat analysis set. Changes within subject over time will be graphically displayed with profile plots.
Measured: 48 months
Tumor Response (RANO).
Measure tumor response to treatment using RANO criteria (Both Phases)
Measured: 48 months
Correlative Studies- Next Generation Sequencing (NGS)
Correlate molecular profiles NGS and HRH1 expression with treatment outcomes. We will correlate molecular profiles (next generation sequencing) with tumor response as sample size allows, by dose level and overall. We will determine if changes in molecular profiles are associated with response using Kruskal-Wallis test or Wilcoxon rank sum test depending on the number of response categories. Expression levels will be correlated with each other using scatterplots and Spearman correlation. Mutational status will be assessed with frequency and percentage for each response category. Fisher's exact test will be used to determine whether there is an association between common mutations and response.
Measured: 48 months
Correlative Studies- MGMT Status
Correlate molecular profiles MGM and HRH1 expression with treatment outcomes. We will correlate molecular profiles (MGMT) with tumor response as sample size allows, by dose level and overall. We will determine if changes in molecular profiles are associated with response using Kruskal-Wallis test or Wilcoxon rank sum test depending on the number of response categories. Expression levels will be correlated with each other using scatterplots and Spearman correlation. Mutational status will be assessed with frequency and percentage for each response category. Fisher's exact test will be used to determine whether there is an association between common mutations and response.
Measured: 48 months
Biological Changes-Exosome HRH1
Evaluate changes in exosome HRH1 during treatment.
Measured: 48 months
Biological Changes-Ki67cells
Evaluate changes in Ki67 during treatment. The focused analysis will be done on the Ki67 cells in pre and post D-Brom dosage and levels associated with OS and PFS. Specifically, the Kaplan-Meier method will estimate OS and PFS distributions by median levels of Ki67 cells, pre-Brom dosage, with comparisons using the log-rank test. Cox regression will also consider Ki67 cellsas a time varying covariate (using the 3 time points collected) of OS and PFS. These analyses will be done by dose level and separately for the window of opportunity study (if sample size allows).
Measured: 48 months
Biological Changes-CD8
Evaluate changes in CD8 during treatment. The focused analysis will be done on the CD8 cells in pre and post D-Brom dosage and levels associated with OS and PFS. Specifically, the Kaplan-Meier method will estimate OS and PFS distributions by median levels of CD8 cells, pre-Brom dosage, with comparisons using the log-rank test. Cox regression will also consider CD8 cells as a time varying covariate (using the 3 time points collected) of OS and PFS. These analyses will be done by dose level and separately for the window of opportunity study (if sample size allows).
Measured: 48 months
Biological Changes-T Cells
Evaluate changes in T-Cells during treatment. The focused analysis will be done on the T cells in pre and post D-Brom dosage and levels associated with OS and PFS. Specifically, the Kaplan-Meier method will estimate OS and PFS distributions by median levels of T cells, pre-Brom dosage, with comparisons using the log-rank test. Cox regression will also consider T cells as a time varying covariate (using the 3 time points collected) of OS and PFS. These analyses will be done by dose level and separately for the window of opportunity study (if sample size allows).
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2026
- Study start1 Jun 2027 (estimated)
- Primary completion1 Jun 2030 (estimated)
- Study completion1 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Grade GliomaStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicole A Shonka, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07859059
- Sponsor's protocol ID
- BROMPH1
- Status last verified
- Sep 2026
- First submitted
- 7 Jul 2025
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Metronomic Temozolomide With Dexbrompheniramine for Patients With Recurrent High-Grade Glioma/Glioblastoma
- ClinicalTrials.gov ID
- NCT07859059
- Acronym / sponsor ID
- BROMPH1
- Conditions
- High Grade Glioma, Glioblastoma, Gliosarcoma
- Keywords
- Recurrent
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 1 Jun 2027 (estimated)
- Primary completion
- 1 Jun 2030 (estimated)
- Study completion
- 1 Jun 2031 (estimated)
- First posted
- 5 Oct 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 goal of this clinical trial is to: 1) evaluate the safety, tolerability, and recommended dose of dexbrompheniramine when combined with metronomic temozolomide for adults with recurrent high-grade glioma who have been previously treated with standard of care chemoradiation therapy and 2) determine the efficacy of the combination therapy in adults with glioblastoma who progressed during the first six cycles of adjuvant standard dose temozolomide.
The main questions it aims to answer are:
- What medical problems to participants have when taking dexbrompheniramine together with temozolomide?
- What is the correct dose of dexbrompheniramine to use when evaluating the safety and efficacy of the combination therapy?
- Is the combination therapy more effective at delaying disease progression compared to temozolomide alone?
Participants will take dexbrompheniramine and temozolomide every day at night.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I: Dose Finding | Experimental | Drug: Dexbrompheniramine, Drug: TemozolomideParticipants receive daily dexbrompheniramine (either 4 mg, 6 mg, or 8 mg) together with 50mg/m2/day temozolomide for up to one year or until progression or intolerance. |
| Arm II: Treatment | Experimental | Drug: Dexbrompheniramine, Drug: TemozolomideParticipants receive daily dexbrompheniramine at the recommended phase 2 dose together with 50mg/m2/day temozolomide for up to one year or until progression or intolerance. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Pathologically proven diagnosis of high grade (aka grade 3 or 4) glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, glioblastoma, gliosarcoma).
- Patients must have received prior radiation therapy and standard temozolomide. Patients who have received any number of additional therapies for previous progressions will be considered eligible. Use of concurrent Optune is allowed.
- 1. Proven glioblastoma/gliosarcoma (2021 WHO criteria) that progressed after standard chemoradiation within the first six cycles of adjuvant TMZ.
- Must be three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression.
- Age ≥ 19 years of age
Key exclusion criteria (9 listed)
- Any significant illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of oral dexbrompheniramine, or put the study outcomes at undue risk.
- Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
- Immunotherapy, chemotherapy, radiotherapy, corticosteroids (at dosages equivalent to prednisone > 20 mg/day) or experimental therapy within 4 weeks before the first dose of study drug
- Any other active malignancy other than nonmelanoma skin cancer or controlled prostate cancer
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 |
|---|---|---|
| DexbrompheniramineAlso: ALA-HIST-IRAntihistamine, HRH1 antagonist | Drug | Arm I: Dose Finding, Arm II: Treatment |
| TemozolomideAlso: TemodarDNA Alkylating Agent | Drug | Arm I: Dose Finding, Arm II: Treatment |
Primary outcome
Safety and RP2D of Combination Therapy
Time frame: 24 months
Evaluate toxicity and determine the recommended dose of dexbrompheniramine with metronomic temozolomide in subjects with recurrent grade 3 and grade 4 glioma.
Efficacy (PFS) of Combination Therapy
Time frame: 48 months
Evaluate efficacy (PFS) of the recommended dose of dexbrompheniramine with metronomic temozolomide in subjects with glioblastoma/gliosarcoma who progress during their first six cycles of adjuvant standard dose temozolomide. (Phase II)
10 secondary outcomes
To measure blood concentration of dexbrompheniramine with temozolomide
Time frame: 24 months
Efficacy (PFS, OS, TTF)
Time frame: 48 months
Examine quality of life changes using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30.)
Time frame: 48 months
Tumor Response (RANO).
Time frame: 48 months
Correlative Studies- Next Generation Sequencing (NGS)
Time frame: 48 months
Correlative Studies- MGMT Status
Time frame: 48 months
Biological Changes-Exosome HRH1
Time frame: 48 months
Biological Changes-Ki67cells
Time frame: 48 months
Biological Changes-CD8
Time frame: 48 months
Biological Changes-T Cells
Time frame: 48 months
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 5 Oct 2026.
- 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.
Nicole A Shonka, MD principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dexbrompheniramine and Temozolomide in people with High Grade Glioma and Glioblastoma, run by University of Nebraska 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 14 inclusion and 9 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 5 Oct 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 combined 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.
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 IIT Office (402-559-4596, IITOffice@unmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and RP2D of Combination Therapy (time frame: 24 months). 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 5 Oct 2026.