GlioblastomaPhase 2NCT07003542
A Phase 2 and Pharmacodynamic Study of Sitagliptin in Patients With Progressive Grade 4 Gliomas
A Phase 2 study testing Sitagliptin in people with Glioblastoma and Brain Tumor, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Brain Tumor
- What is being tested?
- Sitagliptin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Mar 2026to Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 35Show fewer
- 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:
- No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
- In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin.
- Women of childbearing potential must have a negative pregnancy test within 21 days of study entry. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 30 days after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while taking part in this study, she should inform her treating physician immediately. Men of reproductive potential treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 30 days after the last dose of study drug.
- Participants must be able to swallow whole tablets.
- Participants must have the following minimum intervals from prior treatments:
- surgery - 4 weeks
- nitrosoureas - 6 weeks
- cytotoxic chemotherapy - standard intervals depending on the most recent regimen. E.g., for temozolomide 23 days after most recent dose.
- For drugs not listed, the research nurse, treating investigator, and principal investigator will decide on the appropriate interval.
- Investigational therapy or non-cytotoxic therapy - 2 weeks.
- For bevacizumab - 4 weeks from expected date of protocol surgery
- Participants positive for human immunodeficiency virus (HIV) are allowed on study (note: HIV testing is not required), but HIV-positive participants must have:
- An undetectable viral load within 6 months of registration.
- A stable regimen of highly active anti-retroviral therapy (HAART)
- No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
- For participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load Note: Known positive test for HCV ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy.
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Note: A known positive test for HBV surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Participants who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g., participants immunized against hepatitis B)
- Patient must be deemed by investigator to be a candidate for post-operative chemotherapy.
- Participants must have the ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute
Cleveland, Ohio, 44195
David Peereboom, MD, 866-223-8100, TaussigResearch@ccf.org
David Peereboom, MD
About this study
Official title: Targeting Macrophage Migration Inhibitory Factor: A Phase 2 and Pharmacodynamic Study of Sitagliptin in Patients With Progressive Grade 4 Gliomas
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).
Read the 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
- Being tested
- Sitagliptin
- Keywords
- Myeloid-derived suppressor cells
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SitagliptinDrug
Sitagliptin will be self-administered orally by participants.
Dose level - sitagliptin
- 1 100 mg daily
- -1 50 mg daily
- -2 25 mg daily
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Presurgical and post surgical treatment with sitagliptin | Experimental | Not described Receives: Drug: Sitagliptin |
| Group 2: Post surgical treatment with sitagliptin | Experimental | Not described Receives: Drug: Sitagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in tumor CD8+ T cell count between the participants randomized to pre-surgical sitagliptin versus the participants randomized to no pre-surgical treatment.
Measured: Up to day 1 postsurgical
Secondary outcomes (4)
Progression-free survival rate at 6 months
Measured: 6 months post intervention
Overall survival at 12 months
Measured: 12 months post intervention
Overall survival rate after sitagliptin administration concurrent with chemotherapy for progressive GBM.
Measured: 12 months post intervention
Number of adverse events
CTCAEv5.0 adverse events observed with standard dose Sitagliptin administration concurrent with chemotherapy for progressive GBM.
Measured: Up to 30 days after treatment has been discontinued or until death, whichever occurs first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2025
- Study start16 Mar 2026
- Primary completionJun 2027 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized in a 2:1 ratio to the pre-surgical sitagliptin and no pre-surgical treatment groups.
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Peereboom, MD, Principal investigator, Case Comprehensive Cancer Center, Cleveland Clinic Taussig Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07003542
- Sponsor's protocol ID
- CASE2325
- Status last verified
- Aug 2026
- First submitted
- 21 May 2025
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Macrophage Migration Inhibitory Factor: A Phase 2 and Pharmacodynamic Study of Sitagliptin in Patients With Progressive Grade 4 Gliomas
- ClinicalTrials.gov ID
- NCT07003542
- Acronym / sponsor ID
- CASE2325
- Conditions
- Glioblastoma, Brain Tumor
- Keywords
- Myeloid-derived suppressor cells
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 16 Mar 2026 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 4 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants will be randomized in a 2:1 ratio to the pre-surgical sitagliptin and no pre-surgical treatment groups.
| Arm | Type | Receives |
|---|---|---|
| Group 1: Presurgical and post surgical treatment with sitagliptin | Experimental | Drug: Sitagliptin |
| Group 2: Post surgical treatment with sitagliptin | Experimental | Drug: Sitagliptin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (35 listed)
- 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%
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SitagliptinSitagliptin will be self-administered orally by participants. Dose level - sitagliptin * 1 100 mg daily * -1 50 mg daily * -2 25 mg daily | Drug | Group 1: Presurgical and post surgical treatment with sitagliptin, Group 2: Post surgical treatment with sitagliptin |
Primary outcome
Difference in tumor CD8+ T cell count between the participants randomized to pre-surgical sitagliptin versus the participants randomized to no pre-surgical treatment.
Time frame: Up to day 1 postsurgical
4 secondary outcomes
Progression-free survival rate at 6 months
Time frame: 6 months post intervention
Overall survival at 12 months
Time frame: 12 months post intervention
Overall survival rate after sitagliptin administration concurrent with chemotherapy for progressive GBM.
Time frame: 12 months post intervention
Number of adverse events
Time frame: Up to 30 days after treatment has been discontinued or until death, whichever occurs first.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Glioblastoma
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
David Peereboom, MD principal investigator
Case Comprehensive Cancer Center, Cleveland Clinic Taussig Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sitagliptin in people with Glioblastoma and Brain Tumor, run by Case Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 35 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David Peereboom, MD (1-866-223-8100, TaussigResearch@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in tumor CD8+ T cell count between the participants randomized to pre-surgical sitagliptin versus the participants randomized to no pre-surgical treatment. (time frame: Up to day 1 postsurgical). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026.