a phase i trial of high-dose ascorbate in glioblastoma multiforme

Conditions: Glioblastoma; GBM; Glioblastoma Multiforme

Summary: 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.

Eligibility criteria:
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

Keywords: ascorbate ascorbic acid vitamin c radiation temozolomide