Bevacizumab and Ascorbic Acid in Patients Treating With Recurrent High Grade Glioma

This phase I trial studies the side effects and best dose of ascorbic acid when given together with bevacizumab in treating patients with high grade glioma that has come back (recurrent). Monoclonal antibodies, such as bevacizumab may interfere with the ability of tumor cells to grow and spread. Ascorbic acid contains ingredients that may prevent or slow the growth of high grade glioma. Giving bevacizumab and ascorbic acid together may work better in treating patients with high grade glioma.

PRIMARY OBJECTIVES:

I. To evaluate the toxicities and determine the recommended dose of intravenous ascorbic acid given three times weekly in combination with intravenous bevacizumab every two weeks 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 bevacizumab.

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

III. To evaluate progression-free and overall survival of patients with recurrent high grade glioma treated with therapy with ascorbic acid and bevacizumab. Patients with stable or responsive disease after every 2 cycles will continue on therapy with ascorbic acid and bevacizumab until intolerance or progressive disease.

IV. To descriptively examine quality of life (QOL) using European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire 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 (at least 24 hours apart) and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 1 year.

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 who have received additional therapies for previous progressions will be considered eligible
* 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) \>= 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 transaminase (AST) and alanine transaminase (ALT) less than 1.5 times the upper limits of normal
* Serum alkaline phosphatase less than 2.5 times the upper limits of normal
* 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 bevacizumab or ascorbic acid
* Known human immunodeficiency virus (HIV)-positivity AND actively being treated with highly active antiretroviral 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
* Prior hypersensitivity to bevacizumab or toxicity requiring discontinuation of bevacizumab
* Clinically significant cardiovascular disease defined as follows:

  * Inadequately controlled hypertension (i.e., systolic blood pressure \[SBP\] \> 160 mm Hg and/or diastolic pressure \[DBP\] \> 90 mm Hg despite antihypertensive therapy)
  * History of cerebrovascular accident (CVA) within 6 months
  * Myocardial infarction or unstable angina within 6 months
* Evidence or history of bleeding diathesis (greater than normal risk of bleeding, i.e., Hereditary Hemorrhagic Telangiectasia type I or HHT-1) or coagulopathy in the absence of therapeutic anti-coagulation or any hemorrhage/bleeding event \> grade 3 within 4 weeks prior to registration; note: patients with full-dose anticoagulants are eligible provided the patient has been on a stable dose for at least 2 weeks of low molecular weight heparin; therapeutic Coumadin and aspirin doses \> 325 mg daily are not allowed
* Active wound, a serious or non-healing wound, an active ulcer or untreated bone fracture
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =\< 6 months prior to registration
* Major surgical procedure, open biopsy or significant traumatic injury =\< 28 days prior to registration
* 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