Pilot Study of a Metabolic Nutritional Therapy for the Management of Primary Brain Tumors

Summary: The current standard of care for glioblastoma multiforme (GBM), the most common primary brain tumor in adults, includes surgical resection, radiation and chemotherapy. Survival rarely exceeds 18 months. The investigators propose to test the hypothesis that brain tumor cells are unable to utilize ketones as a source of energy when deprived of glucose, due to mitochondrial dysfunction, whereas normal glia and neurons can survive this metabolic stress. A nutritionally adequate but energy restricted, ketogenic diet (ERKD) to deprive brain tumors of energy and resulting in death of glioma cells is promising. ERKD-based therapy to manage brain cancer is both biologically plausible and supported by data in animal models. A multidisciplinary team of oncologists, registered dietitians, and physiologists will implement an ERKD therapy in newly diagnosed GBM subjects. After initial maximal tumor excision, ERKD therapy will be initiated for subjects during a one week inpatient admission to Sparrow Hospital or as a local outpatient and supervised by registered dietitians experienced in implementing this therapy.The ERKD will continue as adjunctive therapy along with radiation therapy and standard of care chemotherapy. The supervised ERKD will continue for an additional 6 weeks after completion of radiation therapy along with the standard of care chemotherapy. The objective of this trial is to determine whether the ERKD decreases tumor size or results in no recurrence in individuals with GBM as measured by serial MRI imaging. Enzymes and signaling pathways that regulate metabolism and cell growth will be assessed in initial and post-ERKD tumors using standard biochemical approaches.

• Inclusion Criteria:
• Adult subjects over age 18 with biopsy proven GBM diagnosis
• Measurable disease after standard therapies
• Eastern Cancer Oncology Group performance status < or =2; and
• Life expectancy >3 months.

Exclusion criteria

• Diagnosis of diabetes mellitus that is being treated by medication
• Concomitant use of glucocorticosteroids
• Cholecystectomy within 1 year prior to study entry
• Inability to adhere to or tolerate dietary protocol
• Active malignancy other than primary brain tumor requiring therapy
• Participation in an investigational study within 2 weeks prior to study entry; Major co-morbidities such as liver, kidney or heart failure that in the judgment of the investigators would disqualify the subject from the trial
• Pregnancy
• Inability to give informed consent