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.
Subjects must have histologically or cytologically confirmed WHO grade 4 glioma for which disease recurrence/progression after first line therapy 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
Prior treatment toxicities not resolved to ≤ Grade 1 according to NCI CTCAE Version 5.0 except for alopecia and neuropathy.
Subjects receiving any other investigational agents.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to sitagliptin or bevacizumab.
Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Single group
Sitagliptin
DrugSitagliptin, PO dose to be determined by Phase I dose de-escalation, cycle length 28 days. Treatment until progression.
Bevacizumab
Biological/VaccineBevacizumab, IV, 10 mg/kg days 1 and 15 every 28 days, until progression.
Phase Ib: Dose-limiting toxicities as measured by CTCAE v5.0
A dose limiting toxicity (DLT) is defined as any of the following sitagliptin-related adverse event (AE) that occurs during the DLT period (first day of treatment through completion of cycle 2 of therapy; each cycle is 28 days), graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
Pilot: Change in participants' concentration of circulating MDSCs with treatment
A two-sided p-value for a test of the null hypothesis, that the ΔPost-Pre in MDSCs is equal to 0 versus the alternative, that it is not equal to 0, will be computed using a one-sample test. In addition, the mean and two-sided 95% confidence interval will be reported.
Event-free survival (EFS)
Time from study treatment initiation to progression which precludes surgery, recurrence or death due to any cause
Overall survival (OS)
Time from study treatment initiation to death due to any cause
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Kailin Yang, MD, PhD
Lead sponsor
University of Iowa
Sponsor institution
