Treatment of Recurrent Brain Tumors: Metabolic Manipulation Combined With Radiotherapy

Inclusion Criteria: * Willingness and ability to participate in diet/metformin intervention for the 8 week period. * Patients must have a previously histologically or cytologically confirmed glioma (astrocytic or oligodendroglial supratentorial tumors grades 2, 3 or 4 according to the WHO 2007 classification 82) that has been previously treated with fractionated radiation therapy and now shows evidence of recurrence. There is no limit regarding the number / type of previous therapies that the patient has received for glioma, aside from exceptions mentioned below. If the brain tumor is in an eloquent location (e.g. brain stem) a clinical diagnosis is sufficient. * Patients must have recovered from the toxic effects of prior therapy. * Patients must have recovered from the effects of any prior surgery to any part of the body. There must be a minimum of 10 days from the day of surgery to the day of registration. For core or needle biopsy, a minimum of 7 days must have elapsed prior to registration. * Patients may have previously undergone more than one craniotomy. * Prior treatment with cytotoxic and biological agents is permissible. There should be at least a 2 week break between prior treatment and enrollment. * Prior treatment with fractionated radiation therapy (up to 66Gy) is an eligibility criterion, however this should have been completed ≥ 4 weeks prior to enrollment. * One prior single fraction radio-surgical procedure within the treatment field is acceptable if V12\<5cc (V12 is the volume of brain receiving 12 or more Gy). Additional radio-surgical procedures outside of the treatment area are acceptable. * Age \>=18 years. * ECOG performance status \<2 (Karnofsky\>60%). * Life expectancy of greater than 2 months. * Patients must have normal organ and marrow function as defined below: * -leukocytes \>2,000/mcL * -absolute neutrophil count \>1,200/mcL * -platelets \>80,000/mcL * -AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal * No contra-indications of metformin use: * Metformin allergy * Renal failure, creatinine levels over 150 μmol/l (1.7 mg/dL) * Liver disease * Current alcohol abuse * Women of childbearing potential must have a negative β-HCG pregnancy test documented within 14 days of registration. * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Known to suffer from one of the following metabolic disorders (all rare): * Carnitine deficiency (primary) * Carnitine palmitoyltransferase (CPT) I or II deficiency * Carnitine translocase deficiency * β-oxidation defects * Medium-chain acyldehydrogenase deficiency (MCAD) * Long-chain acyl dehydrogenase deficiency (LCAD) * Short-chain acyl dehydrogenase deficiency (SCAD) * Long-chain 3-hydroxyacyl-CoA deficiency * Medium-chain 3-hydroxyacyl-CoA deficiency. * Pyruvate carboxylase deficiency * Porphyria * Patients receiving insulin or oral medication on a daily basis for diabetes mellitus * Known severe dyslipidemia: total cholesterol \>400 mg/dl, LDL cholesterol \> 300 mg/dl, triglycerides \> 500 mg/dl * Contraindications to metformin use: * Metformin allergy * Renal failure: creatinine levels over 150 μmol/l (1.7 mg/dL) * Liver disease * Current alcohol abuse