A Phase 2 Trial of High-Dose Ascorbate in Glioblastoma Multiforme

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.