This study is for men and women with recurrent glioblastoma. The purpose of the study is to see if adding immune therapy drugs to usual radiation therapy can shrink or stabilize brain cancer.

This trial is for newly diagnosed glioblastoma (GBM) patients who, after surgery or biopsy, are good candidates for radiation therapy (RT) and temozolomide (TMZ) treatments. The purpose of this study is to see how safe and how well a medical device called Optune works together with the other standard of care treatments for GBM (RT and TMZ). Optune is a device that uses Tumor Treating Fields (TTFields) which are low intensity electric fields that interfere with the division process of cancer cells. Optune has been approved for the treatment of recurrent and newly diagnosed GBM by the Food and Drug Administration (FDA) in the United States. Participants in this study will be randomly assigned to one of two groups:
-The Experimental Group: TTFields using the Optune system upfront with RT and TMZ followed by the use of Optune and TMZ
-The Control Group: Beginning treatment of RT and TMZ, followed by the use of Optune and TMZ
Patients will have clinic visits every 4 weeks and continue on TTFields for 24 months until their disease gets worse or they or their doctor decided to stop treatment.

Glioblastoma adaptive, global, innovative learning environment or GBM AGILE trial is to identify effective therapies and improve survival for a type of brian cancer called glioblastoma (GBM) and to match effective therapies with adult patients with newly diagnosed or recurring glioblastoma. Eligible participants will have a 50/50 chance of taking either standard therapy medications or a medication not yet approved by the FDA called regorafenib during their standard of care treatment for GBM.