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

This is an interventional treatment trial for Glioblastoma Read More

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