Targeting Macrophage Migration Inhibitory Factor: A Phase 2 and Pharmacodynamic Study of Sitagliptin in Patients With Progressive Grade 4 Gliomas
Case Comprehensive Cancer Center
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).
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 ther…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Participants must have histologically or cytologically confirmed WHO grade 4 glioma (including tumors with molecularly defined grade 4 astrocytoma) for whom a clinically-indicated tumor resection is planned. 2. Participants must not have received sitagliptin or other gliptins. 3. Participants must, in the opinion of the investigator be able to tolerate a pre-operative dexamethasone dose of 4 mg/d or the equivalent dose of an alternate glucocorticoid. 4. Age \>18 years 5. Karnofsky performance status ≥ 60% 6. Participants must have adequate organ function and laboratory…
Interventions
- DrugSitagliptin
Sitagliptin will be self-administered orally by participants. Dose level - sitagliptin * 1 100 mg daily * -1 50 mg daily * -2 25 mg daily
Location
- Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer InstituteCleveland, Ohio