NCT07226453

Target Validation and Efficacy of Metformin in Patients With Posterior Fossa Group A (PFA) Ependymoma

A Target Validation and Efficacy Study of Metformin in Patients With Recurrent or Progressive Posterior Fossa Group A (PFA) Ependymoma

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 1 Year – 39 Years
• Healthy volunteers: Not accepted

Summary

This is a multi-site study of the pharmacodynamic effects and efficacy of metformin in children and young adults with recurrent or progressive Posterior Fossa Group A (PFA) ependymoma.

Detailed description

PRIMARY OBJECTIVES: I. To assess pharmacodynamic effect on PFA tumor cells of metformin in participants with recurrent or progressive PFA undergoing surgical resection of the tumor by determining change in H3K27me3 and/or EZHIP expression in tumor nuclei compared to pre-treatment levels (TV Phase) II. To measure disease stabilization rate by Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria (complete (CR), partial (PR) response; ≥50% reduction in size but \<CR), and Stable (SD); \< 50% reduction in size but not meeting criteria for progressive disease) in participants with recurrent or progressive PFA ependymoma following metformin treatment (Efficacy Phase). EXPLORATORY OBJECTIVES: I. Estimate the 1-year progression-free survival and overall-survival of participants with recurrent or progressive PFA treated with single agent metformin (Efficacy Phase). II. To assess pharmacokinetics (PK) of metformin by measuring plasma, CSF and intra-tumoral concentration of metformin, the latter two obtained at the time of surgery or at the time of further disease progression on study in consenting participants (Both cohorts). III. Evaluate the feasibility of using MR spectroscopy (MRS) imaging to study oncometabolite profile of recurrent or progressive PFA ependymoma pre-and post-treatment with metformin. OUTLINE: This will be a two-part study: a TV phase and an efficacy phase. Participants will be initially enrolled in the TV phase and receive treatment prior to planned surgery. Participants already enrolled on the TV phase may continue to the efficacy phase of the study if they have measurable disease post-surgery. Participants in the efficacy phase will receive daily oral metformin until disease progression or till there are unacceptable adverse event(s). Long term/survival follow-up procedures are to be captured under the Pediatric Neuro-Oncology Consortium (PNOC) Protocol for Children and Young Adults Diagnosed with a Central Nervous System (CNS) Tumor to Assess Cognitive, Quality of Life (QOL), and Comprehensive Effects of Therapies protocol (COMP). Participants will be followed under the PNOC COMP protocol until death or withdrawal from study.

Conditions

• Posterior Fossa Ependymal Tumor

Interventions

Type	Name	Description
DRUG	Metformin	Given orally (PO)
PROCEDURE	Planned Surgical Resection	Undergo planned surgery as part of regular care
PROCEDURE	Magnetic Resonance Imaging (MRI)	Undergo MRI imaging
PROCEDURE	Specimen Collection	Tumor Tissue, blood, and cerebral spinal fluid (CSF) may be collected for correlative analysis.
PROCEDURE	MR spectroscopy (MRS)	Undergo MRS imaging

Timeline

• Start date: 2026-05-04
• Primary completion: 2028-04-30
• Completion: 2030-03-31
• First posted: 2025-11-10
• Last updated: 2026-04-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study