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

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.