Marizomib for RELA-Fusion and Non-RELA-Fusion Recurrent Ependymoma

Background: * Ependymomas are rare primary brain tumors arising from radial glial stem cells. They comprise 5.2% of all pediatric primary brain tumors and 1.9% of all adult primary brain tumors. * The standard therapy for newly diagnosed ependymoma is gross total resection followed by radiation therapy. For anaplastic ependymoma, recurrence rate is high with a median progression free survival (PFS) of 2.3 years. * There are limited chemotherapy options for recurrent ependymomas, which have already been irradiated. Therefore, there is an unmet need to target novel pathways for treatment of ependymomas. * About 70% of supratentorial ependymomas have a characteristic signature C11 orf95-V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA) fusion which drives tumorigenesis in ependymomas by activating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB) transcription pathway. * Marizomib is a second-generation irreversible proteasome inhibitor which penetrates across the blood-brain-barrier (BBB). It inhibits the activity of 20S proteasome in glioma cells, activates caspases, builds up reactive oxygen species and thus induces apoptosis. Marizomib blocks the NF-pathway by proteasome inhibition. Thus, it may have an additional targeted therapeutic effect in the RELA-fusion molecular subgroup of ependymomas. Objective: -To evaluate the efficacy of treatment with marizomib in RELA-fusion recurrent ependymoma and non RELA-fusion recurrent ependymoma as measured by progression-free survival at 6 months (PFS6). Eligibility: * Histologically proven intra-cranial or spinal ependymoma. * Radiographic evidence of tumor progression * Patients must be greater than or equal to 18 years old. Patients must have had prior radiotherapy. Design: * This is a phase II study to determine the efficacy of marizomib in recurrent ependymoma. * A novel 2-stage sequential design will be employed to conduct the trial for recurrent ependymoma. * In the first stage, we will enroll 18 patients with RELA-fusion ependymoma and if 4 or more patients in Cohort 1 are progression free at 6 months, we will proceed to stage 2; otherwise, we will terminate the trial and conclude that marizomib is not effective. * In the second stage, we will enroll 32 patients with non RELA-fusion ependymoma. * Patients will be treated with marizomib in cycles consistent of 28 days until disease progression or a maximum of 24 cycles.