This is a phase 1 (first in man) study testing the safety of adding high dose ascorbate (vitamin C) to standard radiation and chemotherapy for initial treatment of glioblastoma multiforme (GBM).

This phase 1 study will test the safety of adding high dose ascorbate (vitamin C) to standard chemoradiation and, after the radiation is completed, during 6 cycles of temozolomide.

Standard treatment for glioblastoma multiforme (GBM) involves surgery followed by radiation combined with temozolomide (a chemotherapy). After radiation, patients receive cycles of temozolomide (adjuvant chemotherapy)

Participants will:

• receive high doses of intravenous (IV) ascorbate three times a week during chemoradiation
• receive high doses of intravenous (IV) ascorbate twice a week during adjuvant chemotherapy (after radiation)

This is a phase 1 study will evaluate the side effects of adding this drug to the standard therapy. The dose given to a participant will be determined by how well other participants have tolerated the drug.

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.

• Age ≥ 18 years

• ECOG performance status 0-2 (Karnofsky > 50%).

• A complete blood count and differential must be obtained within 21 days prior to the first dose of radiation, with adequate bone marrow functions as defined below:

  • Absolute neutrophil count (ANC) ≥ 1500 cells per mm3
  • Platelets ≥ 100,000 per mm3
  • Hemoglobin ≥ 8 g/dL

• Serum blood chemistries within 21 days before the first day of radiation, as defined below:

  • Creatinine ≤ 2.0 mg
  • Total bilirubin ≤ 1.5 mg/dL
  • ALT (Alanine Aminotransferase)≤ 3 times the institutional upper limit of normal
  • AST (Aspartate Aminotransferase) ≤ 3 times the institutional upper limit of normal

• Tolerate one text dose (15g) of ascorbate

• Not pregnant

• Ability to understand and willingness to sign a written informed consent document

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

Individual participant data is shared through an NIH/NCI approved data sharing plan in compliance with subject's consent to sharing. Investigators interested in IPD should contact the sponsor, study PI, or study coordinator for more information.

Study protocol, SAP, and ICF will be shared at conclusion of the study.

Investigators interested in IPD should contact the sponsor, study PI, or study coordinator for more information. IRB approval for the recipient investigator may be required, as determined by the individual data received.