Sitagliptin in Recurrent/Progressive Grade 4 Glioma

NCT07541781 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202512310
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glioma; Glioblastoma; Recurrent Glioma; Recurrent Glioblastoma; Grade 4 Malignant Glioma of Brain (Disorder)

Outcome Measures

Primary Outcomes (2)

• 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

  First day of treatment through completion of cycle 2 of therapy (each cycle is 28 days)

• 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.

  From pre- to post-treatment (end of post-op cycle 1; each cycle is 28 days).

Secondary Outcomes (2)

• Event-free survival (EFS)

  From study treatment initiation through three years

• Overall survival (OS)

  From study treatment initiation through three years

Study Arms (1)

Standard of care Bevacizumab in addition to Sitagliptin

EXPERIMENTAL

Phase I: Bevacizumab in combination with Sitagliptin Phase Ib: 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 on non-surgical patients with recurrent GBM Pilot: 12 patients with recurrent GBM, will receive pre-operative treatment with sitagliptin for at least 5 days at the MTD determined in phase 1b. These patients will then undergo surgical resection of the tumor. All patients will receive postoperative sitagliptin in addition to standard-of-care bevacizumab

Drug: Sitagliptin; Biological: Bevacizumab

Interventions

Sitagliptin DRUG

Sitagliptin, PO dose to be determined by Phase I dose de-escalation, cycle length 28 days. Treatment until progression.

Standard of care Bevacizumab in addition to Sitagliptin

Bevacizumab BIOLOGICAL

Bevacizumab, IV, 10 mg/kg days 1 and 15 every 28 days, until progression.

Also known as: Avastin

Standard of care Bevacizumab in addition to Sitagliptin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Hemoglobin ≥ 9 g/dl
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Total bilirubin \< 1.5 x institutional upper limit of normal (ULN)
• AST (SGOT) ≤ 3 X institutional ULN
• ALT (SGPT) ≤ 3 X institutional ULN
• Calculated creatinine clearance \> 50 mL/min
• Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio. For UPC ratio \> 0.5, 24-hour urine protein must be obtained and must be \< 1000 mg.
• Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria:

You may not qualify if:

• The presence of any of the following will exclude a subject from study enrollment:
• 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, bevacizumab, or other chemotherapy agents.
• 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.
• Known HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with sitagliptin and/or bevacizumab. In addition, these subjects are at increased risk of lethal infections when treated with marrow suppressive therapy.
• Other malignancy within the past 2 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or vulva; c) prostate cancer of Gleason Score 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder, or benign tumors of the adrenal or pancreas.
• Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events Version 5.0 \[CTCAE v.5.0\] diarrhea of any etiology at screening).
• Known active infection with hepatitis B or hepatitis C virus.
• Pregnant or breastfeeding.
• Subjects who receive insulin or sulfonylurea for diabetes mellitus.
• Subjects with history of type 1 diabetes, uncontrolled type 2 diabetes, hypoglycemia requiring medical intervention, or those who are deemed not suitable to receive sitagliptin at the discretion of the investigators.
• Unable or unwilling to swallow tablets.
• Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that would, in the Investigator's judgment, make the patient inappropriate for this study.
• Arterial ischemic event (e.g., unstable angina, myocardial infarction, stroke) within 6 months of study entry.

Sponsors & Collaborators

• Kailin Yang, MD, PhD: lead

Study Sites (1)

University of Iowa Health Care

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

Sitagliptin Phosphate; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Kailin Yang, MD, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kailin Yang, MD, PhD

CONTACT

+1 319 356 3630; kailin-yang@uiowa.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 10, 2026
• First Posted: April 21, 2026
• Study Start (Estimated): May 31, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2030
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)