Health TrialsbyHealthPanel

Metronomic Temozolomide With Dexbrompheniramine for Recurrent High-Grade Glioma/Glioblastoma

ConditionsHigh Grade GliomaGlioblastomaGliosarcoma
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age19+
SponsorUniversity of Nebraska

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Dexbrompheniramine

    Drug

    Antihistamine, HRH1 antagonist

  • Temozolomide

    Drug

    DNA Alkylating Agent

Treatment groups

41 Participants
are divided into 2 treatment groups
Group A: Arm I: Dose FindingExperimental treatment 2 interventions
Group B: Arm II: TreatmentExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
24 months
2

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)

Time frame
48 months

Secondary outcomes

1

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.

Time frame
24 months
2

Efficacy (PFS, OS, TTF)

Estimate progression free survival at 6 and 12 months, overall survival, and time to treatment failure (Both Phases).

Time frame
48 months
3

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.

Time frame
48 months
4

Tumor Response (RANO).

Measure tumor response to treatment using RANO criteria (Both Phases)

Time frame
48 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Nebraska

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: