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

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