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.