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

NCT07003542 | Recruiting Phase 2 DMC

• 1 other identifier: CASE2325
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Glioblastoma; Brain Tumor

Keywords

Myeloid-derived suppressor cells

Outcome Measures

Primary Outcomes (1)

• Difference in tumor CD8+ T cell count between the participants randomized to pre-surgical sitagliptin versus the participants randomized to no pre-surgical treatment.

  Up to day 1 postsurgical

Secondary Outcomes (4)

• Progression-free survival rate at 6 months

  6 months post intervention

• Overall survival at 12 months

  12 months post intervention

• Overall survival rate after sitagliptin administration concurrent with chemotherapy for progressive GBM.

  12 months post intervention

• Number of adverse events

  Up to 30 days after treatment has been discontinued or until death, whichever occurs first.

Study Arms (2)

Group 1: Presurgical and post surgical treatment with sitagliptin

EXPERIMENTAL

Drug: Sitagliptin

Group 2: Post surgical treatment with sitagliptin

EXPERIMENTAL

Drug: Sitagliptin

Interventions

Sitagliptin DRUG

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

Group 1: Presurgical and post surgical treatment with sitagliptin; Group 2: Post surgical treatment with sitagliptin

Eligibility Criteria

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

You may qualify if:

• 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.
• Participants must not have received sitagliptin or other gliptins.
• 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.
• Age \>18 years
• Karnofsky performance status ≥ 60%
• Participants 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 \< 1.5x institutional upper limit of normal (ULN)
• AST (SGOT) ≤ 3x institutional ULN
• ALT (SGPT) ≤ 3x institutional ULN
• Calculated creatinine clearance \> 50 mL/min or creatinine \< 1.5x institutional upper limit of normal (ULN)
• Prothrombin time/international normalized ratio (PT/INR) \< 1.4 for participants not on warfarin.
• Participants on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria:

You may not qualify if:

• Prior treatment toxicities not resolved to ≤ Grade 1 according to NCI CTCAE Version 5.0 except alopecia and neuropathy.
• Participants receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sitagliptin.
• Participants with uncontrolled diabetes mellitus
• Participants who require insulin therapy or a sulfonylurea
• Participants with documented history of hypoglycemia requiring medical intervention or who in the opinion of the investigator are not suitable to receive sitagliptin.
• Participants 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.
• Other prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are excluded. Otherwise, participants with prior or concurrent malignancy are eligible.
• Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 diarrhea of any etiology at screening) (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events Version 5.0 \[CTCAE v.5.0\]).
• Pregnant or breastfeeding.
• 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.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• David Peereboom, MD

  Case Comprehensive Cancer Center, Cleveland Clinic Taussig Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Peereboom, MD

CONTACT

1-866-223-8100; TaussigResearch@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized in a 2:1 ratio to the pre-surgical sitagliptin and no pre-surgical treatment groups.

Study Record Dates

• First Submitted: May 21, 2025
• First Posted: June 4, 2025
• Study Start: August 8, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: August 11, 2025

Record last verified: 2025-08

Locations

US (1)