Temozolomide and Ascorbic Acid in Treating Patients With Recurrent High-Grade Glioma
Condition: Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Anaplastic Oligoastrocytoma; Glioblastoma; Gliosarcoma
MeSH terms: Glioblastoma; Astrocytoma; Gliosarcoma; Oligodendroglioma
Intervention: ascorbic acid; temozolomide; quality-of-life assessment; laboratory biomarker analysis
Intervention description: Given IV; Given PO; Ancillary studies; Correlative studies
Intervention MeSH terms: Ascorbic Acid; Temozolomide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 19 Years
Healthy volunteers: No

Summary:

      This phase I trial studies the side effects and best dose of ascorbic acid when given
      together with temozolomide in treating patients with high-grade glioma that has come back.
      Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth
      of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping
      them from spreading. Ascorbic acid contains ingredients that may prevent or slow the growth
      of high-grade gliomas. Giving temozolomide with ascorbic acid may kill more tumor cells.
    

Eligibility criteria:

        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