Sitagliptin in Recurrent/Progressive Grade 4 Glioma

In this Phase I trial, it is proposed that sitagliptin will be used to inhibit Myeloid Derived Suppressor Cells (MDSCs) in recurrent Glioblastoma (GBM). As this trial designed is for patients with recurrent GBM, patients will receive standard of care, bevacizumab, in addition to sitagliptin. The goal of this trial is to provide the proof of concept that suppressing MDSCs via sitagliptin is safe and feasible in patients with recurrent GBMs. In the Phase Ib component, a standard 3+3 design and dose de-escalation will be used to determine the maximal tolerated dose (MTD) of sitagliptin in combination with bevacizumab in non-surgical patients with recurrent GBM. After completion of the Phase Ib part, the study will proceed to the pilot phase. In the pilot phase component, 12 patients with recurrent GBM, who will receive pre-operative treatment with sitagliptin for at least 5 days at the MTD determined in phase 1b, will be enrolled. These patients will then undergo surgical resection of the tumor. All patients will receive postoperative sitagliptin in addition to standard-of-care bevacizumab. Tumor tissue will undergo dissociation and single-cell sequencing, immune profiling, and whole genome sequencing. The goal of the pilot phase is to obtain preliminary evidence demonstrating a reduction in the concentration of circulating MDSCs after the treatment of sitagliptin and to provide preliminary evidence of sitagliptin in reducing infiltrating MDSCs in the GBM tumor microenvironment. Patients will have their steroid dosing reduced to the equivalence of 4 mg dexamethasone per day or lower for at least 5 days prior to preoperative sitagliptin.