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

Pediatric Brain Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05521984
• Other study ID #: 202210013
• Status: Recruiting
• Phase: Phase 1
• Start date: April 3, 2023
• Est. completion date: November 30, 2026

Study information

• Verified date: May 2024
• Source: Washington University School of Medicine
• Contact: Andrew Cluster, M.D.
• Phone: 314-273-1451
• Email: acluster[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a longitudinal, dose-finding, open label safety and tolerability phase Ib treatment study. The study hypothesis is that dapagliflozin will be well-tolerated by brain tumor patients on chemotherapy as assessed by tolerability and side effect profiles.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: November 30, 2026
• Est. primary completion date: August 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 21 Years

Eligibility

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 between 6 and 21 years old (inclusive)

• Patient is capable of swallowing whole pills

• 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 carmustine, 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, carmustine 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.

Related Conditions & MeSH terms

• Brain Neoplasms
• Pediatric Brain Tumor

Intervention

Drug:
• Dapagliflozin
Commercially available
• Carmustine
Standard of care

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Children's Discovery Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and type of adverse events experienced by participants	-Adverse events will be graded by CTCAE (version 5.0).	From start of treatment through 30 days after last day of dapagliflozin treatment (estimated to be 4 months)
Secondary	Change in blood glucose		From baseline through end of treatment (estimated to be 3 months)
Secondary	Change in ketones		From baseline through end of treatment (estimated to be 3 months)
Secondary	Change in HbA1c		From baseline through end of treatment (estimated to be 3 months)
Secondary	Tumor response rate	Tumor response will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline.; Tumor response rate = number of participants with complete or partial response.	From pre-therapy to post-12 weeks of therapy
Secondary	Feasibility of regimen	-Feasibility is defined as the successful enrollment of a total of 20 evaluable patients to the study within 3 years and the optimal dose of dapagliflozin is at least 5 mg.	Through completion of treatment for all enrolled patients (estimated to be 39 months)
Secondary	Changes in fructosamine		From baseline through end of treatment (estimated to be 3 months)
Secondary	Changes in c-peptide		From baseline through end of treatment (estimated to be 3 months)
Secondary	Changes in glucagon		From baseline through end of treatment (estimated to be 3 months)

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine