A Phase I Trial of High-Dose Ascorbate in Glioblastoma Multiforme

Exclusion Criteria

• •Recurrent high grade glioma
• •G6PD (glucose-6-phosphate dehydrogenase) deficiency
• •Patients actively receiving insulin unless approved by the study medical monitor, study sponsor, and the study principal investigator.
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide.
• •Significant co-morbid central nervous system disease, including but not limited to, multiple sclerosis.
• •Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide. High dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs.
• •Prior invasive malignancies (except non-melanomatous skin cancers and carcinoma in situ of the cervix or bladder) unless disease free for ≥ 5 years.
• •Patients who have received prior chemotherapy (including Gliadel wafers) for the current glioma.
• •Prior radiation therapy to the head or neck, which would result in overlap of radiation therapy fields.
• •Patients may not be receiving any other investigational agents.
• •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• •Pregnant women are excluded from this study because ionizing radiation is a known teratogen, and temozolomide is a Class D agent with the potential for teratogenic or abortifacient effects.
• •Known HIV-positive individuals. High-dose ascorbate acid is a known CYP450 3A4 (an enzyme pathway) inducer, which results in lower serum levels of antiretroviral drugs