Targeting Pediatric Brain Tumors With Sodium Glucose Cotransporter 2 Inhibitors (SGLT2i)

• Status: Not yet recruiting
• Trial end date: 2026-06-30
• Target enrollment: 0
• Participant gender: All

Summary

This is a pilot study of the feasibility and safety of dapagliflozin (in addition to standard of care treatment) for the treatment of pediatric patients with recurrent brain tumors. The primary hypothesis is that dapagliflozin is well-tolerated and safe to use in this patient population. The investigators also hypothesize that dapagliflozin will be efficacious as an adjunct to front-line chemotherapy assessed by decreased tumor markers mediated by its pleiotropic metabolic effects.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine
• Collaborator: Children's Discovery Institute
• Treatments: Carmustine; Dapagliflozin

Criteria

Inclusion Criteria:

• Diagnosis of a recurrent primary brain tumor with no curative therapy available.

• Measurable disease using pediatric Response Assessment in Neuro-Oncology Criteria (RANO) criteria.

• Life expectancy > 12 weeks.

• Prior treatment with radiation alone, chemotherapy alone or combined radiation and chemotherapy is allowed.

• Patient is < 21 years of age.

• Normal bone marrow and organ function as defined below:

• Leukocytes ≥ 3,000/mcL

• Absolute neutrophil count ≥ 1,500/mcl

• Platelets ≥ 100,000/mcl

• Total bilirubin ≤ 1.5 x IULN

• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

• Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

• Normal room air oxygenation must be documented. If room air oxygen saturation is less than 97%, a diffusion capacity of carbon monoxide (DLCO) of greater than 80%, must be demonstrated.

• Karnofsky or Lansky performance score of ≥ 60

• Patients of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a female patient become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legal guardian/legally authorized representative, if applicable).

Exclusion Criteria:

• Current or previous treatment with SGLT2i or thiazolidinedione.

• Current use of high dose dexamethasone (exceeding 4 mg/day). Seven days prior to start of dapagliflozin and BCNU, patients receiving dexamethasone must be on a stable or decreasing dose (≤ 0.1 mg/kg/day or maximum 4 mg/day). Note that it is preferred that patients not be on dexamethasone during the study.

• A history of other malignancy with the exceptions of malignancies for which all treatment was completed at least 2 years before registration with no evidence of disease and locally treated skin squamous or basal cell carcinoma.

• Type 1 diabetes or current insulin treatment.

• History of stroke or transient ischemic attack (in the last 5 years).

• HbA1c > 8.5%. The rationale is that this is the level that would require addition of insulin. However, insulin use is excluded in this study due to the increased risk of ketoacidosis.

• Currently receiving any other investigational agents.

• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to dapagliflozin, BCNU or other agents used in the study.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, peripheral arterial disease, ketoacidosis, severe kidney disease (estimated glomerular filtration rate eGFR < 30 mL/min/1.73m2), symptomatic hypotension, and chronic/frequent urinary tract infections or yeast infections.

• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.

• Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.