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

Prior treatment

• 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
• 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.

Other illness

• 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
• Any other active malignancy other than nonmelanoma skin cancer or controlled prostate cancer
• Known history of intolerance to antihistamines due to glaucoma or urinary retention

Other

• Lactating or pregnant

• 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.
• 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.