Targeting Pediatric Brain Tumors and Relapsed/Refractory Solid Tumors With Sodium Glucose Cotransporter 2 Inhibitors (SGLT2i)
This is a pilot phase Ib study of the safety of dapagliflozin (in addition to standard of care treatment) for the treatment of pediatric patients with recurrent brain tumors and relapsed/refractory solid 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.
• Diagnosis of a recurrent primary brain tumor with no curative therapy available OR diagnosis of relapsed/refractory solid tumor with no curative option and has trialed past a second line of therapy.
• Measurable disease per the following:
‣ For patients with brain tumors: measurable disease pediatric Response Assessment in Neuro-Oncology Criteria (RANO) criteria
⁃ For patients with solid tumors: measurable disease using response evaluation criteria in solid tumors (RECIST 1.1). Includes patients with diagnoses of relapsed or refractory sarcomas, neuroblastoma, and Wilms tumor. Other rare solid tumors can be discussed with study chair.
• 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 m\^2 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 and their partners must agree to use two forms of acceptable contraception (including one barrier method) prior to study entry and for the duration of study participation. Should a female patient or partner of a male 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. Legally authorized representatives may sign and give informed consent on behalf of study participants. All patients and/or their parents or legal guardians must sign an IRB approved written informed consent document.