Ependymoblastoma

This research is being done to find out more information about a brain tumor called Embryonal Tumor with Multilayer Rosettes (ETMR) by collecting medical information from children who have this disease.
The purpose of this research study is to create and maintain a research database for patients with ETMR. The database will include information about occurrence rates, patient information, tumor tissue information, and response to treatment. This will help advance our understanding of this rare disease.
In addition, this study will include obtaining survival data and evaluating therapeutic response to expert consensus therapy, and procuring patient tumor tissue.

Approximately 90% of children with malignant brain tumors that have recurred or relapsed after receiving conventional therapy will die of disease. Despite this terrible and frustrating outcome, continued treatment of this population remains fundamental to improving cure rates. Studying this relapsed population will help unearth clues to why conventional therapy fails and how cancers continue to resist modern advances. Moreover, improvements in the treatment of this relapsed population will lead to improvements in upfront therapy and reduce the chance of relapse for all. Novel therapy and, more importantly, novel approaches are sorely needed. This trial proposes a new approach that evaluates rational combination therapies of novel agents based on tumor type and molecular characteristics of these diseases. The investigators hypothesize that the use of two predictably active drugs (a doublet) will increase the chance of clinical efficacy. The purpose of this trial is to perform a limited dose escalation study of multiple doublets to evaluate the safety and tolerability of these combinations followed by a small expansion cohort to detect preliminary efficacy. In addition, a more extensive and robust molecular analysis of all the participant samples will be performed as part of the trial such that we can refine the molecular classification and better inform on potential response to therapy. In this manner the tolerability of combinations can be evaluated on a small but relevant population and the chance of detecting antitumor activity is potentially increased. Furthermore, the goal of the complementary molecular characterization will be to eventually match the therapy with better predictive biomarkers.
PRIMARY OBJECTIVES:
To determine the safety and tolerability and estimate the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of combination treatment by stratum.
To characterize the pharmacokinetics of combination treatment by stratum.
SECONDARY OBJECTIVE:
To estimate the rate and duration of objective response and progression free survival (PFS) by stratum.