Methotrexate Infusion Into Fourth Ventricle in Children With Recurrent Malignant Fourth Ventricular Brain Tumors

The goal of this clinical research study is to establish the maximum tolerated dose (MTD) of direct administration of methotrexate into the fourth ventricle of the brain in patients with recurrent malignant brain tumors including medulloblastoma, primitive neuroectodermal tumors (PNET), atypical teratoid/rhabdoid tumors (AT/RT), and ependymoma. Methotrexate is designed to block cancer cells from dividing, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.

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 be used for the infusion of methotrexate directly into the 4th ventricle of the brain, which is 1 of 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 3 cycles of intraventricular methotrexate into the fourth ventricle. Each cycle will be of 4 weeks duration. During the first 3 weeks (Day 1-7 weekly) methotrexate will be infused twice weekly on days 1 and 4 (+/-2 days). The 4th week will be a rest week. Methotrexate 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 infusion should last about 3 minutes each time. If the participant already has an ommaya catheter, methotrexate will begin after an MRI has confirmed adequate cerebrospinal fluid flow. Study Visits: Prior to Cycle 1: * Medical history will be reviewed and any updates to health will be recorded * A physical with vital signs and neurological exam will be done. * Blood (about 1 teaspoon) will be drawn for routine test * A MRI scan of the brain and spine will be done to check the status of the disease. On the days of Methotrexate Infusion: * A physical with vital signs and neurological exam will be done * A Ommaya reservoir tap (a catheter is placed into the Ommaya reservoir to give the methotrexate infusion). * Cerebrospinal fluid (about 1 teaspoon) will be collected for routine tests. Within 7 days of completing Cycle 3: * A physical with vital signs and neurological exam will be done. * A lumbar puncture will be done. * A MRI scan of the brain and spine will be done to check the status of the disease. Length of Study: The participant will receive up to 3 cycles of the methotrexate, 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 investigational study. Methotrexate is FDA approved and commercially available for infusion directly into brain tumors. The infusion of methotrexate into the 4th ventricle of the brain is investigational, Up to 18 patients will be enrolled in this study. All will be enrolled at Children's Memorial Hermann Hospital.