Targeting Pediatric Brain Tumors and Relapsed/Refractory Solid Tumors With Sodium Glucose Cotransporter 2 Inhibitors (SGLT2i)

NCT05521984 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202210013
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pediatric Brain Tumor; Pediatric Solid Tumor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Change in blood glucose

  From baseline through end of treatment (estimated to be 3 months)

• Change in ketones

  From baseline through end of treatment (estimated to be 3 months)

• Change in HbA1c

  From baseline through end of treatment (estimated to be 3 months)

• Changes in fructosamine

  From baseline through end of treatment (estimated to be 3 months)

• Changes in c-peptide

  From baseline through end of treatment (estimated to be 3 months)

Study Arms (4)

Brain Cancer: Dapagliflozin + Standard of Care Chemotherapy (Ages 6-10)

EXPERIMENTAL

* Dapagliflozin will be initiated by mouth once daily at the same time as standard of care chemotherapy (carmustine). * Dapagliflozin 5 mg by mouth once daily on days 1-84 (duration of study) * All patients will stop taking dapagliflozin after 12 weeks of treatment.

Drug: Dapagliflozin; Drug: Carmustine

Brain Cancer: Dapagliflozin + Standard of Care Chemotherapy (Ages 11-21)

EXPERIMENTAL

* Dapagliflozin will be initiated by mouth once daily at the same time as standard of care chemotherapy (carmustine). * Dapagliflozin will be initiated at 5 mg by mouth once daily, days 1-4 (2 weeks) * Dapagliflozin will be escalated to 10 mg by mouth once daily for the remaining 10 weeks (after consultation with study endocrinologist) * All patients will stop taking dapagliflozin after 12 weeks of treatment.

Drug: Dapagliflozin; Drug: Carmustine

Solid Tumor Cancer: Dapagliflozin + Standard of Care Chemotherapy (Ages 6-10)

EXPERIMENTAL

* Dapagliflozin will be initiated by mouth once daily at the same time as standard of care chemotherapy (topotecan + cyclophosphamide). * Dapagliflozin 5 mg by mouth once daily on days 1-84 (duration of study) * All patients will stop taking dapagliflozin after 12 weeks of treatment. * Each cycle is 21 days.

Drug: Dapagliflozin; Drug: Topotecan; Drug: Cyclophosphamide

Solid Tumor Cancer: Dapagliflozin + Standard of Care Chemotherapy (Ages 11-21)

EXPERIMENTAL

* Dapagliflozin will be initiated by mouth once daily at the same time as standard of care chemotherapy (topotecan + cyclophosphamide). * Dapagliflozin will be initiated at 5 mg by mouth once daily, days 1-4 (2 weeks) * Dapagliflozin will be escalated to 10 mg by mouth once daily for the remaining 10 weeks (after consultation with study endocrinologist) * All patients will stop taking dapagliflozin after 12 weeks of treatment. * Each cycle is 21 days.

Drug: Dapagliflozin; Drug: Topotecan; Drug: Cyclophosphamide

Interventions

Dapagliflozin DRUG

Commercially available

Brain Cancer: Dapagliflozin + Standard of Care Chemotherapy (Ages 11-21); Brain Cancer: Dapagliflozin + Standard of Care Chemotherapy (Ages 6-10); Solid Tumor Cancer: Dapagliflozin + Standard of Care Chemotherapy (Ages 11-21); Solid Tumor Cancer: Dapagliflozin + Standard of Care Chemotherapy (Ages 6-10)

Carmustine DRUG

Standard of care

Brain Cancer: Dapagliflozin + Standard of Care Chemotherapy (Ages 11-21); Brain Cancer: Dapagliflozin + Standard of Care Chemotherapy (Ages 6-10)

Topotecan DRUG

Standard of care

Solid Tumor Cancer: Dapagliflozin + Standard of Care Chemotherapy (Ages 11-21); Solid Tumor Cancer: Dapagliflozin + Standard of Care Chemotherapy (Ages 6-10)

Cyclophosphamide DRUG

Standard of care

Solid Tumor Cancer: Dapagliflozin + Standard of Care Chemotherapy (Ages 11-21); Solid Tumor Cancer: Dapagliflozin + Standard of Care Chemotherapy (Ages 6-10)

Eligibility Criteria

• Age: 6 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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, 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 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/1.73m\^2), 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 prior to first dose of dapagliflozin.
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Children's Discovery Institute: collaborator

Study Sites (1)

Washington University School of Medicine/St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

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

MeSH Terms

Interventions

dapagliflozin; Carmustine; Topotecan; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Camptothecin; Alkaloids; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds

Study Officials

• Andrew Cluster, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew Cluster, M.D.

CONTACT

314-273-1451; acluster@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2022
• First Posted: August 30, 2022
• Study Start: April 3, 2023
• Primary Completion (Estimated): March 31, 2031
• Study Completion (Estimated): June 30, 2031
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)