NCT07003542

A Phase 2 and Pharmacodynamic Study of Sitagliptin in Patients With Progressive Grade 4 Gliomas

Targeting Macrophage Migration Inhibitory Factor: A Phase 2 and Pharmacodynamic Study of Sitagliptin in Patients With Progressive Grade 4 Gliomas

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: Case Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate whether treating glioblastoma patients with sitagliptin can improve immune response against the tumor by targeting specific immune cells called myeloid-derived suppressor cells (MDSCs) that suppress your body's natural immune response against cancer. Sitagliptin is an investigational drug for this condition that works by inhibiting an enzyme called dipeptidyl peptidase 4 (DPP-4), which MDSCs rely on to enter the brain and function. While sitagliptin is FDA-approved for diabetes treatment, its use in glioblastoma is investigational (experimental).

Detailed description

The glioblastoma microenvironment is well known to be immunosuppressive. One mechanism of immunosuppression involves systemic and local accumulation of myeloid-derived suppressor cells (MDSCs) that inhibit cytotoxic immune cell populations and contribute to immune suppression. Glioblastoma(GBM) patients have increased circulating MDSCs compared to lower grade glioma patients, and GBM patients with a better prognosis have reduced MDSCs in their tumors as well as in their peripheral circulation. A trial (NCT02669173) performed at the Cleveland Clinic demonstrated that pre-surgical anti-MDSC therapy (capecitabine) was associated with reduced circulating MDSCs and increased cytotoxic immune infiltration in tumor tissue. This proof-of-principle pilot study demonstrated that targeting MDSCs in patients can attenuate tumor-induced immunosuppression. Subsequent work at the Cleveland Clinic demonstrated that MDSCs relied on dipeptidyl peptidase 4 (DPP-4) for entry into the brain and overall MDSC function. Screening for a DPP-4 inhibitor identified sitagliptin as a good inhibitor that has limited toxicity with efficacy in pre-clinical models. Investigators hypothesize that treating GBM patients with sitagliptin will deplete circulating MDSCs and reduce their entry into the brain, reversing systemic and intratumoral immunosuppression. To test this hypothesis, investigators plan a "window of opportunity" clinical trial to evaluate the safety and biological impact of sitagliptin treatment in patients with recurrent grade 4 glioma undergoing clinically indicated surgical resection. For this trial, investigators will enroll 48 patients; 36 will undergo presurgical treatment with sitagliptin and 12 with no presurgical treatment. All patients will receive post-operative sitagliptin and chemotherapy until disease progression.

Conditions

• Glioblastoma
• Brain Tumor

Interventions

Type	Name	Description
DRUG	Sitagliptin	Sitagliptin will be self-administered orally by participants. Dose level - sitagliptin * 1 100 mg daily * -1 50 mg daily * -2 25 mg daily

Timeline

• Start date: 2025-08-08
• Primary completion: 2027-06-01
• Completion: 2028-06-01
• First posted: 2025-06-04
• Last updated: 2025-08-11

Locations

1 site across 1 country: United States