Treatment of Recurrent Brain Tumors: Metabolic Manipulation Combined With Radiotherapy (SMC 0712-13)

This is an interventional treatment trial for Brain Neoplasms focused on measuring Radiotherapy, Ketosis, Metformin, Magnetic Resonance Imaging, Metabolome, Insulin, recurrent brain tumors, gliomas, glioblastomas, astrocytomas Read More

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