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

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

NCT ID: NCT05521984

Condition: Pediatric Brain Tumor

Conditions: Official terms:
Brain Neoplasms
Dapagliflozin
Carmustine

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Dapagliflozin
Description: Commercially available
Arm group label: Dapagliflozin + Standard of Care carmustine chemotherapy (Ages 11-21)
Arm group label: Dapagliflozin + Standard of Care carmustine chemotherapy (Ages 6-10)

Intervention type: Drug
Intervention name: Carmustine
Description: Standard of care
Arm group label: Dapagliflozin + Standard of Care carmustine chemotherapy (Ages 11-21)
Arm group label: Dapagliflozin + Standard of Care carmustine chemotherapy (Ages 6-10)

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.

Criteria for eligibility:
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 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.

Gender: All

Minimum age: 6 Years

Maximum age: 21 Years

Healthy volunteers: No

Locations:

Facility:
Name: Washington University School of Medicine

Address:
City: Saint Louis
Zip: 63110
Country: United States

Status: Recruiting

Contact:
Last name: Andrew Cluster, M.D.

Phone: 314-273-1451
Email: acluster@wustl.edu

Investigator:
Last name: Andrew Cluster, M.D.
Email: Principal Investigator

Investigator:
Last name: Joseph Ippolito, M.D., Ph.D.
Email: Sub-Investigator

Investigator:
Last name: Jennifer Sprague, M.D., Ph.D.
Email: Sub-Investigator

Investigator:
Last name: Linda Peterson, M.D.
Email: Sub-Investigator

Investigator:
Last name: Jingqin (Rosy) Luo, Ph.D.
Email: Sub-Investigator

Start date: April 3, 2023

Completion date: November 30, 2026

Lead sponsor:
Agency: Washington University School of Medicine
Agency class: Other

Collaborator:
Agency: Children's Discovery Institute
Agency class: Other

Source: Washington University School of Medicine

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05521984
http://www.siteman.wustl.edu