A Pilot Study of Ketogenic Diet and Metformin in Glioblastoma: Feasibility and Metabolic Imaging
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
Inclusion Criteria:

 1. Patients must have histologically confirmed high-grade glioma (e.g. glioblastoma,
 gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed
 glioma or other anaplastic gliomas).

 2. 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.

 3. Patients must not have been exposed to bevacizumab.

 4. Patients cannot be taking insulin or other oral hypoglycemic. Must be at least 6 weeks
 from last oral hypoglycemic or insulin.

 5. 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.

 6. Patients must be >18 years old.

 7. Karnofsky performance status >60%.

 8. Life expectancy of greater than 12 weeks.

 9. 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.

 10. 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

 11. Patients having undergone recent resection or progressive tumor will be eligible as
 long as all of the following conditions apply:

 1. They have recovered from the effects of surgery.

 2. On a steroid dosage that has been stable for at least 5 days.

 3. 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.

 12. Patients must have the ability to understand and the willingness to sign a written
 informed consent document.

 Exclusion Criteria:

 1. Patients who are receiving any other investigational agents.

 2. Patients who have had prior therapy with bevacizumab and/or other VEGF inhibitors.

 3. Patients who are taking insulin or other oral hypoglycemic. Must be at least 6 weeks
 from last oral hypoglycemic or insulin.

 4. History of allergic reactions attributed to metformin.

 5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
 infection, symptomatic congestive heart failure, unstable angina pectoris, diabetes
 requiring oral hypoglycemic drugs and/or insulin, cardiac arrhythmia, or psychiatric
 illness/social situations that would limit compliance with study requirements.

 6. Patients known to have a malignancy that has required treatment in the last 12 months
 and/or is expected to require treatment in the next 12 months (except nonmelanoma skin
 cancer or carcinoma in-situ in the cervix).

 7. The effects of a Ketogenic diet or metformin on the developing human fetus are
 unknown. For this reason, women of childbearing 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 she or her partner is participating in this
 study, she should inform her treating physician immediately.

 8. Patients with current alcoholism.