Intervention: Temozolomide
Trial phase: Phase 1
ATC code: L01AX03
SMILES: Cn1nnc2c(C(N)=O)ncn2c1=O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 4
Group description: Patients receive ascorbic acid IV over 90-120 minutes three times per week and temozolomide orally days 1-28. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

ascorbic acid: Given IV

temozolomide: Given PO

quality-of-life assessment: Ancillary studies

laboratory biomarker analysis: Correlative studies
Eligibility criteria:
Inclusion Criteria:

Patients must have pathologically proven diagnosis of high grade glioma
Patients must have received prior radiation therapy and standard temozolomide
Patients must be three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression
Patients must have recovered from toxicity of prior therapy
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 or better
Absolute neutrophil count (ANC) count >= 1,500/mm^3
Hemoglobin >= 8 g/dL
Platelet count >= 100,000/mm^3
Serum creatinine that is at or below 2.0 mg/dL
Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 1.5 times the upper limits of normal; note: if hepatic function is abnormal, the decision to initiate temozolomide treatment should carefully consider the benefits and risks for the individual patient
Serum alkaline phosphatase less than 2.5 times the upper limits of normal; note: if hepatic function is abnormal, the decision to initiate temozolomide treatment should carefully consider the benefits and risks for the individual patient
The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts
Women of reproductive potential must be non-pregnant and non-nursing and must agree to employ an effective barrier method of birth control throughout the study and for up to 6 months following treatment
Women of child-bearing potential must have a negative pregnancy test within 7 days of initiating study; (no childbearing 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)

Exclusion Criteria:

History of uncontrollable allergic reactions to temozolomide or ascorbic acid or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy
Known human immunodeficiency virus (HIV)-positivity AND actively being treated with highly active anti-retroviral therapy (HAART)
History of glucose-6-phosphate dehydrogenase deficiency
History of oxalate nephrolithiasis or urine oxalate > 60 mg/dL
Anuria, dehydration, severe pulmonary congestion or pulmonary edema or fixed low cardiac input since all are conditions for which osmotic diuresis are contraindicated and ascorbic acid has high osmolarity
Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide; note: high dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs
Simultaneous participation in other therapeutic clinical trials will not be allowed
Inability to co-operate with the requirements of the protocol
Pregnant and nursing women are excluded from this study