Targeting Myeloid-Derived Suppressor Cells in Patients With Recurrent/Progressive Grade 4 Glioma: Phase 1 Trial of Sitagliptin
Kailin Yang, MD, PhD
Summary
Sitagliptin, when combined with standard-of-care drug bevacizumab, is being tested to 1) find out if it is effective at treating gliomas that have returned or progressed after treatment, and 2) find out what the highest dose of sitagliptin is appropriate to give when combined with bevacizumab.
Description
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 combin…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: Phase 1b * Subjects must have histologically or cytologically confirmed WHO grade 4 glioma for which disease recurrence/progression is diagnosed by the treating physician. * Subjects must not have received sitagliptin or bevacizumab for this disease. * Age \>18 years * Performance status: ECOG performance status 0-2 * Subjects must have adequate organ function and laboratory parameters within 21 days of study entry as defined below: 1. Hemoglobin ≥ 9 g/dl 2. Absolute neutrophil count ≥ 1,500/mcL 3. Platelet count ≥ 100,000/mcL 4. Total bilirubin \< 1.5 x institut…
Interventions
- DrugSitagliptin
Sitagliptin, PO dose to be determined by Phase I dose de-escalation, cycle length 28 days. Treatment until progression.
- BiologicalBevacizumab
Bevacizumab, IV, 10 mg/kg days 1 and 15 every 28 days, until progression.
Location
- University of Iowa Health CareIowa City, Iowa