This clinical trial evaluates adding high-dose ascorbate (vitamin C) to standard of care treatment of glioblastoma multiforme (a type of brain tumor) in adults. All subjects will receive high-dose ascorbate in addition to the standard treatment.

Standard treatment for glioblastoma multiforme (GBM) involves maximum safe surgical resection followed by radiation combined with temozolomide (a chemotherapy pill you take by mouth). After radiation, patients receive additional cycles of temozolomide (adjuvant chemotherapy).

Participants will:

• receive high doses of intravenous (IV) ascorbate three times a week during the combined radiation and chemotherapy phase
• receive high doses of intravenous (IV) ascorbate twice a week during adjuvant chemotherapy (after radiation)
• complete health-related quality of life questionnaires pre-radiation, 4 weeks into radiation, 4 weeks after radiation, and then every 3 months. In addition, patients will complete neurocognitive testing pre-radiation, 4 weeks into radiation, 4 weeks after radiation, and approximately 9 months after initiating radiation therapy.

The adjuvant chemotherapy portion of this study lasts for 6 months. After that is completed, participants will go back to standard therapy for their cancer. Participants will continue to have life-long follow-up for this study.

Inclusion Criteria:

• Ability to understand and willingness to sign informed consent (power of attorney and/or legally authorized representatives cannot sign on behalf of the patient)
• 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 or biopsy
• Age ≥ 18 years
• ECOG performance status 0-2. (KPS > 50)
• Absolute neutrophil count (ANC) ≥ 1500 cells per mm3
• Platelets ≥ 100,000 per mm3
• Hemoglobin ≥ 8 g/dL
• Creatinine ≤ 2.0 mg
• Total bilirubin ≤ 1.5 mg/dL
• ALT ≤ 3 times the institutional upper limit of normal
• AST ≤ 3 times the institutional upper limit of normal
• Tolerate one test dose (15g) of ascorbate.
• Not pregnant.

Exclusion Criteria:

• Recurrent high grade glioma
• G6PD (glucose-6-phosphate dehydrogenase) deficiency.
• Patients actively receiving insulin or using a finger-stick glucometer daily for blood glucose measurements
• 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: warfarin, flecainide, methadone, amphetamines, quinidine, and chlorpropamide.
• Known active concurrent malignancy, as determined by treating physicians.
• Patients who have received prior chemotherapy (including Gliadel wafers) for the current glioma.
• Prior radiation therapy to the head or neck resulting in overlap of RT fields.
• Patients receiving any other investigational agents (imaging agents are acceptable)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection that would result in a hospital stay or delay of treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or impact patient safety.
• Pregnant women.
• Breastfeeding women.
• Known HIV-positive individuals. High-dose ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs.

Data will be released publicly as per participant consent and IRB approval. Individual researchers should contact the research team for data sharing.

Study protocol and informed consent will be shared after primary completion. Statistical analysis plan will be shared with results reporting.

An IRB-stamped signed usage agreement will be required in addition to a data sharing agreement between the academic centers.