High-Dose Ascorbic Acid in Treating Patients with Newly Diagnosed Glioblastoma Multiforme Receiving Temozolomide and Undergoing Radiation Therapy

Inclusion Criteria

• Patients must have newly diagnosed (i.e., within 5 weeks), histologically or cytologically confirmed glioblastoma multiforme
• Diagnosis must be made by surgical biopsy or excision
• Therapy must begin =< 5 weeks after surgery
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky > 50%)
• Absolute neutrophil count (ANC) >= 1500 cells per mm^3
• Platelets >= 100,000 per mm^3
• Hemoglobin >= 8 g/dL
• Creatinine =< 2.0 mg
• Total bilirubin =< 1.5 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 times the institutional upper limit of normal
• Tolerate one test dose (15 g) of ascorbate
• Not pregnant; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; pregnancy tests will be obtained per physician discretion
• Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

• Recurrent high grade glioma
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• 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; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with temozolomide, breastfeeding should be discontinued if the mother is treated with temozolomide
• Known human immunodeficiency virus (HIV)-positive individuals; high-dose ascorbate acid is a known cytochrome P450 3A4 (CYP450 3A4) inducer, which results in lower serum levels of antiretroviral drugs; a clinical trial designed to address these interaction issues is more appropriate than this phase 1 study