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

Inclusion Criteria

• •1. Participants must have recurrent or progressive posterior fossa A (PFA) ependymoma following surgery AND radiation treatment (RT).
• •2. Participants must have a diagnosis of PFA ependymoma. Any number of previous recurrences are permissible provided the participant meets other enrollment criteria.
• •3. Participants must have adequate tumor tissue available from initial diagnosis or from pre- trial enrollment. Formalin-fixed paraffin-embedded (FFPE) material (1 full block) should be provided. If FFPE material is not available, 10 unstained slides with an accompanying hematoxylin and eosin (H\&E) report should be provided.
• •Target Validation (TV) Phase:
• •o Participants are candidates to undergo elective surgery for removal of all or a portion of their recurrent/progressive tumor.
• •Efficacy Phase:
• •* Participant must have measurable disease; this will be defined as lesions that can be accurately measured in two dimensions (longest diameter to be recorded) The size threshold is met if both in-plane diameters are ≥10 mm or both in-plane diameters are at least two times the MRI slice thickness, plus the interslice gap with a minimum size of no less than double the slice thickness on MRI.
• •* Participants with an isolated local progression of the tumor following RT (or stereotactic radiosurgery, SRS) must be \> 6 months from completion of RT to the lesion to rule out pseudo progression or must have tissue confirmation of progression prior to enrollment.
• •* Previously irradiated lesions are considered non-measurable except in cases of documented progression of the lesion since the completion of radiation therapy as outlined above.
• •4. Prior Therapy: Participants must not be receiving metformin for other medical indications or previous exposure to metformin following their diagnosis of PFA ependymoma. However, participants treated on the TV phase, but did not continue onto maintenance therapy will be allowed to enroll on the efficacy phase with future recurrences or progression of their disease.
• •5. Age: 1 -39 years at the time of enrollment.
• •6. Performance Score: Karnofsky \>= 50 for participants \> 16 years of age and Lansky \>=50 for participants \<=16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• •7. Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration.
• •8. Organ Function Requirements
• •1. Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3.
• •2. Platelet count \>=100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
• •3. Serum creatinine \< 1.5 Upper Limit normal (ULN) based on age and gender
• •4. Total bilirubin \<= 1.5 x ULN for age; in presence of Gilbert's syndrome, total bilirubin \< 3 x ULN or direct bilirubin \< 1.5 x ULN
• •5. alanine aminotransferase (ALT) \<= 3 x ULN.
• •6. aspartate aminotransferase (AST) \<=3 x ULN.
• •9. Participants with seizure disorder may be enrolled if well controlled and are on stable dose of anti-seizure medication for \> 72 hours prior to enrollment. Participants who have neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
• •10. Participants must enroll on PNOC COMP if PNOC COMP is open to accrual at the enrolling institution.
• •11. A legal parent/guardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.