This is a trial for adults who have a diagnosis of a malignant (cancerous) brain tumor and have either been newly diagnosed with glioblastoma and completed standard chemotherapy and radiation or have a recurrence of glioblastoma (the tumor has come back).   

The purpose of this study is to assess the safety of an investigational drug Paxalisib in conjunction with a ketogenic diet (a high fat, low carbohydrate diet) and Metformin (a drug approved by the Food and Drug Administration to treat type 2 diabetes), and to see what effects it has on glioblastoma. Paxalisib has not yet been FDA-approved to treat glioblastoma or other cancers.
   
This research study is being done because current data shows that Paxalisib may have a favorable response for prolonging stable disease (when the tumor does not grow significantly). Paxalisib is involved in inhibiting the pathways involved with cell division and cell growth that are activated in cancer.
   
The ketogenic diet has a lower ratio of carbohydrates and higher levels of fat and protein when compared with a regular diet. Many forms of the ketogenic diet are commercially available and mass-consumed for weight loss, and they are not known to have either a negative or positive impact on the life expectancy of the consumers. There is no evidence that the ketogenic diet may inhibit or stimulate tumor growth, however, it is known that a ketogenic diet can suppress the levels of blood sugar (glucose) and insulin in humans. Insulin is a hormone that is needed to regulate or reduce blood glucose. Glucose is thought to be a contributor to tumor growth so it is hypothesized that by using ketogenic diet to suppress the levels of glucose, tumor growth might be suppressed as well. Additionally, early data suggests it can significantly reduce seizures.

 Studies have shown that Metformin has the potential to increase the benefits of the ketogenic diet if taken together.
   
 There will be two groups participating in this study. One group (Cohort 1) is for patients that have newly diagnosed GBM and have completed standard chemotherapy and radiation. The other group (Cohort 2) is for patients that have recurrent glioblastoma.
   
Regardless of the group, participants will be given the study drug called Paxalisib, as well as Metformin, and will follow a ketogenic diet throughout the study.