Clinical Trial Finder

Inclusion Criteria:

• - Patients must have pathologically proven diagnosis of high grade glioma.

• - Patients must have received prior radiation therapy and standard temozolomide.

• - Patients must be three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression.

• - Patients must have recovered from toxicity of prior therapy.

• - Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 or better.

• - Absolute neutrophil count (ANC) count >= 1,500/mm^3.

• - Hemoglobin >= 8 g/dL.

• - Platelet count >= 100,000/mm^3.

• - Serum creatinine that is at or below 2.0 mg/dL.

• - Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 1.5 times the upper limits of normal; note: if hepatic function is abnormal, the decision to initiate temozolomide treatment should carefully consider the benefits and risks for the individual patient.

• - Serum alkaline phosphatase less than 2.5 times the upper limits of normal; note: if hepatic function is abnormal, the decision to initiate temozolomide treatment should carefully consider the benefits and risks for the individual patient.

• - The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts.

• - Women of reproductive potential must be non-pregnant and non-nursing and must agree to employ an effective barrier method of birth control throughout the study and for up to 6 months following treatment.

• - Women of child-bearing potential must have a negative pregnancy test within 7 days of initiating study; (no childbearing potential is defined as age 55 years or older and no menses for two years or any age with surgical removal of the uterus and/or both ovaries)

  Exclusion Criteria:

  - History of uncontrollable allergic reactions to temozolomide or ascorbic acid or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy.

• - Known human immunodeficiency virus (HIV)-positivity AND actively being treated with highly active anti-retroviral therapy (HAART) - History of glucose-6-phosphate dehydrogenase deficiency.

• - History of oxalate nephrolithiasis or urine oxalate > 60 mg/dL.

• - Anuria, dehydration, severe pulmonary congestion or pulmonary edema or fixed low cardiac input since all are conditions for which osmotic diuresis are contraindicated and ascorbic acid has high osmolarity.

• - Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.

• - Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide; note: high dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs.

• - Simultaneous participation in other therapeutic clinical trials will not be allowed.

• - Inability to co-operate with the requirements of the protocol.

- Pregnant and nursing women are excluded from this study

PRIMARY OBJECTIVES:

• I. To evaluate the toxicities and determine the recommended dose of intravenous ascorbic acid given three times weekly in combination with temozolomide in patients with recurrent high grade glioma.

SECONDARY OBJECTIVES:

• I. To evaluate changes in the levels of serum ascorbic acid using high-performance liquid chromatography (HPLC) with coulometric electrochemical detection) during therapy with ascorbic acid and temozolomide.

• II. Radiographic assessment of disease status after 2 cycles of therapy with ascorbic acid and temozolomide.

• III. To evaluate progression-free and overall survival of patients with recurrent high grade glioma treated with therapy with ascorbic acid and temozolomide.

• IV. To descriptively examine quality of life (QOL) using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 during treatment.

OUTLINE: This is a dose-escalation study of ascorbic acid. Patients receive ascorbic acid intravenously (IV) over 90-120 minutes three times per week and temozolomide orally days 1-28. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 2 months for 1 year and then periodically thereafter.

Arms

Experimental: Treatment (ascorbic acid, temozolomide)

Patients receive ascorbic acid IV over 90-120 minutes three times per week and temozolomide orally days 1-28. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Interventions

Dietary Supplement: - ascorbic acid

Given IV

Drug: - temozolomide

Given PO

Other: - quality-of-life assessment

Ancillary studies

Other: - laboratory biomarker analysis

Correlative studies