A Pilot Study of Ketogenic Diet and Metformin in Glioblastoma: Feasibility and Metabolic Imaging
This clinical trial is for men and women with high-grade gliomas. Glucose (sugar) is thought to be a contributor to tumor growth. The ketogenic diet (a high fat, low carbohydrate diet) and metformin (a drug approved by the Food and Drug Administration to treat type 2 diabetes) are both known to lower blood glucose levels. The purpose of the study is to evaluate the tolerability of a ketogenic diet in conjunction with metformin and whether maintaining and the diet with metformin will have any effect on participants. Participants will prepare their own meals with the help of a nutritionist. Participants will continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects
• Patients must have histologically confirmed high-grade glioma (e.g. glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed glioma or other anaplastic gliomas).
• Patients must have an MRI performed within 21 days prior to beginning the study diet and on a fixed dose of steroids for at least 5 days. If the steroid dose is increased between the date of imaging and registration, a new baseline MR/CT is required.
• Patients must not have been exposed to bevacizumab.
• Patients cannot be taking insulin or other oral hypoglycemic. Must be at least 6 weeks from last oral hypoglycemic or insulin.
• Must not have known type 1 or type 2 diabetes and expected to need either insulin and/or an oral hypoglycemic agents within the next 6 months.
• Patients must be \>18 years old.
• Karnofsky performance status \>60%.
• Life expectancy of greater than 12 weeks.
• Patients must have normal organ and marrow function as defined below:
‣ Leukocytes \>3,000/mcL
⁃ Absolute neutrophil count \>1,000/mcL
⁃ Platelets \>100,000/mcL
⁃ Total bilirubin \<2.0 X institutional upper limit of normal (unless known to have Gilbert's Disease)
⁃ AST (SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal
⁃ Serum Glucose: \< 200 mg/dL
⁃ Creatinine \< 1.5 mg/dL (for males), \< 1.4 mg/dL (for females), or within normal lab limits OR
⁃ Creatinine clearance \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
⁃ Patients must not have any significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patients' ability to tolerate this therapy
⁃ Patients having undergone recent resection or progressive tumor will be eligible as long as all of the following conditions apply:
• They have recovered from the effects of surgery.
∙ On a steroid dosage that has been stable for at least 5 days.
∙ Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease postoperatively, a MRI should be done:
‣ No later than 96 hours in the immediate post-operative period or
⁃ At least 4 weeks post-operatively, and
⁃ Within 14 days of registration, and
⁃ If the 96-hour scan is more than 21 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required on a stable steroid dosage for at least 5 days.
⁃ Patients must have the ability to understand and the willingness to sign a written informed consent document.