[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100658920":3},{"organization":4,"outcomesModule":7,"designInfo":49,"detailedDescription":48,"studyPopulation":48,"armGroups":55,"interventions":67,"overallOfficials":81,"centralContacts":85,"locations":94,"responsibleParty":113,"collaborators":48,"id":115,"slug":116,"hasResults":117,"nctId":118,"briefTitle":119,"officialTitle":120,"acronym":48,"eligibilityCriteria":121,"healthyVolunteers":117,"sex":122,"minAge":123,"maxAge":48,"enrollmentInfo":124,"targetDuration":48,"studyType":127,"phases":128,"briefSummary":131,"conditions":132,"keywords":136,"overallStatus":138,"whyStopped":48,"lastUpdateSubmitDate":139,"lastUpdatePostDateStruct":140,"startDateStruct":143,"completionDateStruct":145,"leadSponsor":147,"locationsCount":148},{"fullName":5,"class":6},"University of Nebraska","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":17,"otherOutcomes":48},[9,13],{"measure":10,"description":11,"timeFrame":12},"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.","24 months",{"measure":14,"description":15,"timeFrame":16},"Efficacy (PFS) of Combination Therapy","Evaluate efficacy (PFS) of the recommended dose of dexbrompheniramine with metronomic temozolomide in subjects with glioblastoma\u002Fgliosarcoma who progress during their first six cycles of adjuvant standard dose temozolomide. (Phase II)","48 months",[18,21,24,27,30,33,36,39,42,45],{"measure":19,"description":20,"timeFrame":12},"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.",{"measure":22,"description":23,"timeFrame":16},"Efficacy (PFS, OS, TTF)","Estimate progression free survival at 6 and 12 months, overall survival, and time to treatment failure (Both Phases).",{"measure":25,"description":26,"timeFrame":16},"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.",{"measure":28,"description":29,"timeFrame":16},"Tumor Response (RANO).","Measure tumor response to treatment using RANO criteria (Both Phases)",{"measure":31,"description":32,"timeFrame":16},"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.",{"measure":34,"description":35,"timeFrame":16},"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.",{"measure":37,"description":38,"timeFrame":16},"Biological Changes-Exosome HRH1","Evaluate changes in exosome HRH1 during treatment.",{"measure":40,"description":41,"timeFrame":16},"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).",{"measure":43,"description":44,"timeFrame":16},"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).",{"measure":46,"description":47,"timeFrame":16},"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).",null,{"allocation":50,"interventionModel":51,"interventionModelDescription":48,"primaryPurpose":52,"observationalModel":48,"timePerspective":48,"maskingInfo":53},"NON_RANDOMIZED","PARALLEL","TREATMENT",{"masking":54,"maskingDescription":48,"whoMasked":48},"NONE",[56,63],{"label":57,"type":58,"description":59,"interventionNames":60},"Arm I: Dose Finding","EXPERIMENTAL","Participants receive daily dexbrompheniramine (either 4 mg, 6 mg, or 8 mg) together with 50mg\u002Fm2\u002Fday temozolomide for up to one year or until progression or intolerance.",[61,62],"Drug: Dexbrompheniramine","Drug: Temozolomide",{"label":64,"type":58,"description":65,"interventionNames":66},"Arm II: Treatment","Participants receive daily dexbrompheniramine at the recommended phase 2 dose together with 50mg\u002Fm2\u002Fday temozolomide for up to one year or until progression or intolerance.",[61,62],[68,75],{"type":69,"name":70,"description":71,"armGroupLabels":72,"otherNames":73},"DRUG","Dexbrompheniramine","Antihistamine, HRH1 antagonist",[57,64],[74],"ALA-HIST-IR",{"type":69,"name":76,"description":77,"armGroupLabels":78,"otherNames":79},"Temozolomide","DNA Alkylating Agent",[57,64],[80],"Temodar",[82],{"name":83,"affiliation":5,"role":84},"Nicole A Shonka, MD","PRINCIPAL_INVESTIGATOR",[86,91],{"name":87,"role":88,"phone":89,"phoneExt":48,"email":90},"IIT Office","CONTACT","402-559-4596","IITOffice@unmc.edu",{"name":92,"role":88,"phone":89,"phoneExt":48,"email":93},"Taylor A Johnson, MA","taylora.johnson@unmc.edu",[95],{"facility":96,"status":48,"city":97,"state":98,"zip":99,"country":100,"countryCode":101,"cosmosGeoPoint":102,"geoPoint":107,"contacts":108},"University of Nebraska Medical Center","Omaha","Nebraska","68198","United States","US",{"type":103,"coordinates":104},"Point",[105,106],-95.94043,41.25626,{"lat":106,"lon":105},[109],{"name":110,"role":88,"phone":111,"phoneExt":48,"email":112},"Michaela K Savine, RN","1(402)836-9488","misavine@unmc.edu",{"type":114,"investigatorFullName":48,"investigatorTitle":48,"investigatorAffiliation":48,"oldNameTitle":48,"oldOrganization":48},"SPONSOR","100658920","phase-1-metronomic-temozolomide-with-dexbrompheniramine-for-recurrent-high-grade-gliomaglioblastoma-100658920",false,"NCT07859059","Metronomic Temozolomide With Dexbrompheniramine for Recurrent High-Grade Glioma\u002FGlioblastoma","A Phase I\u002FII Study of Metronomic Temozolomide With Dexbrompheniramine for Patients With Recurrent High-Grade Glioma\u002FGlioblastoma","Inclusion Criteria (Phase I)\n\n1. Pathologically proven diagnosis of high grade (aka grade 3 or 4) glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, glioblastoma, gliosarcoma).\n2. 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.\n\nInclusion Criteria (Phase II)\n\n1\\. Proven glioblastoma\u002Fgliosarcoma (2021 WHO criteria) that progressed after standard chemoradiation within the first six cycles of adjuvant TMZ.\n\nInclusion Criteria (Both Phases)\n\n1. Must be three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression.\n2. Age ≥ 19 years of age\n3. Recovery from toxicity of any prior therapy that in the opinion of the investigator could impact tolerance to the study drug.\n4. Adequate performance status: ECOG ≤ 2\n5. Adequate organ function:\n\n   * bone marrow reserve: (ANC ≥ 1,500 mm3, hemoglobin ≥ 8 g\u002FdL, platelet count ≥ 100,000 mm3\n   * renal function: (serum creatinine ≤ 2.0 mg\u002FdL)\n   * hepatic function: serum AST and ALT \\\u003C 1.5 ULN, serum alkaline phosphatase \\\u003C 2.5 ULN)\n6. 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\u002For both ovaries) A negative pregnancy test is required within 7 days of initiating the study\n7. 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.\n8. 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.\n\nExclusion Criteria\n\n1. 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.\n2. 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\n3. 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\n4. Immunotherapy, chemotherapy, radiotherapy, corticosteroids (at dosages equivalent to prednisone \\> 20 mg\u002Fday) or experimental therapy within 4 weeks before the first dose of study drug\n5. Any other active malignancy other than nonmelanoma skin cancer or controlled prostate cancer\n6. Lactating or pregnant\n7. Known history of intolerance to antihistamines due to glaucoma or urinary retention\n8. 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\n9. 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.","ALL","19 Years",{"count":125,"type":126},41,"ESTIMATED","INTERVENTIONAL",[129,130],"PHASE1","PHASE2","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.\n\nThe main questions it aims to answer are:\n\n* What medical problems to participants have when taking dexbrompheniramine together with temozolomide?\n* What is the correct dose of dexbrompheniramine to use when evaluating the safety and efficacy of the combination therapy?\n* Is the combination therapy more effective at delaying disease progression compared to temozolomide alone?\n\nParticipants will take dexbrompheniramine and temozolomide every day at night.",[133,134,135],"High Grade Glioma","Glioblastoma","Gliosarcoma",[137],"Recurrent","NOT_YET_RECRUITING","2026-09-29",{"date":141,"type":142},"2026-10-05","ACTUAL",{"date":144,"type":126},"2027-06-01",{"date":146,"type":126},"2031-06-01",{"name":5,"class":6},1]