The goal of this clinical research study is to establish the safety of direct administration of 5-Azacytidine into the fourth ventricle of the brain or resection cavity in patients with recurrent posterior fossa ependymoma.

If the participant is eligible to take part in this study, the participant will have surgery to place a catheter into the Ommaya reservoir. The Ommaya reservoir is a catheter system that allows drugs to be administered directly to parts of the brain. This catheter will used for the infusion of 5-Azacytidine directly into the 4th ventricle of the brain, which is 1 or the 4 connected fluid-filled cavities in the brain.

If the study doctor thinks it is necessary, based on the location of the tumor, the tumor may also be removed while the participant is already under anesthesia just before the catheter is placed.

Study Drug Administration:

The participant will receive 12 weekly (+/- one day) 10 mg infusions of 5-Azacytidine.

5-Azacytidine will be infused through the Ommaya reservoir catheter directly into the 4th ventricle of the brain starting at a minimum of 7 days after the catheter placement surgery. A MRI will be done to confirm adequate cerebrospinal fluid flow. The 5-Azacytidine infusion will last 2-3 minutes.

If the participant already has an Ommaya catheter, 5-Azacytidine will begin after an MRI has confirmed adequate cerebrospinal fluid flow.

Study Visits:

Prior to first infusion:

Medical history will be reviewed and any updates to health will be recorded. Physical and Neurological exam with vital signs will be done. Blood (about 1 teaspoon) will be drawn for routine test. A lumbar puncture will be done. A MRI scan of the brain and spine will be done to check the status of the disease.

On the days of the 5-Azacytidine Infusion:

A neurological exam with vital signs will be done. A Ommaya reservoir tap (a catheter is placed into the Ommaya reservoir to give the 5-Azacytidine infusion.

Cerebrospinal fluid (about 1 teaspoon) will be collected for routine tests.

Within 7 days of completing the Final infusion:

A neurological exam with vital signs will be done. A lumbar puncture will be done. A MRI scan of the brain and spine will be done to check status of the disease.

Length of Study:

The participant will receive 12 infusions of 5-Azacytidine, as long as the doctor thinks it is in their best interest. The participant will no longer be able to receive the study drug if the disease gets worse, if intolerable side effects occur, or if unable to follow study directions.

This is an investigation study. 5-Azacytidine is FDA approved and commercially available to be given subcutaneous or into the bloodstream (intravenously) but has never been given in the 4th ventricle of the brain. The infusion of 5-Azacytidine into the 4th ventricle of the brain is investigational.

Up to 10 patients will be enrolled in this study. All will be enrolled at Children's Memorial Hermann Hospital

Inclusion Criteria:

• Diagnosis: Patients with histologically verified ependymoma, with recurrence or progression involving anywhere in the brain and/or spine. To be eligible, patients' disease must have originated in the posterior fossa of the brain.
• Patient must have either measurable or evaluable tumor as assessed by MRI of the brain and total spine.
• An implanted catheter in the fourth ventricle or posterior fossa tumor cavity attached to a ventricular access device or agreement to have one placed.
• A minimum of 7 days between last dose of systemic chemotherapy and/or radiation therapy and first infusion of 5-Azacytidine into fourth ventricle.
• Life expectancy of at least 12 weeks in the opinion of the PI
• Lansky score of 50 or greater if ≤16 years of age or Karnofsky score of 50 or greater if > 16 years of age.
• Existing neurological deficits must have been stable for a minimum of 1 week prior to study enrollment.
• Patients must have recovered from the acute toxic effects of all prior anticancer chemotherapy
• Adequate bone marrow function defined by peripheral absolute neutrophil count (ANC) ≥ 500/µL, platelet count ≥ 50,000/ µL (transfusion independent), and hemoglobin ≥9.0 gm/dL (may receive RBC transfusions)
• Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent.

Exclusion Criteria:

• Enrolled in another treatment protocol
• Has received another investigational or chemotherapy agent or radiation therapy within 7 days prior to 5-Azacytidine infusion into the fourth ventricle.
• Evidence of untreated infection
• Pregnant of lactating women