View clinical trials related to Medulloblastoma, WNT-activated.
Filter by:This clinical study is going to be done on a type of brain tumor in children called Medulloblastoma. The WNT pathway type of medulloblastoma is considered to be low risk and have the best outcomes in terms of survival. With the current standard of care for this type of medulloblastoma it is believed by the investigators that we are over treating the disease and increasing the long term side effects of these children. Several groups in the world are testing de-intensification of treatment in this favourable subset of children who experience long term late side effects of therapy. By reducing the dose to the craniospinal axis and keeping the total tumor bed dose the same in this study the investigators are expecting to reduce some of the late side effects of craniospinal irradiation without compromising disease control and survival.
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.