A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma

Historically, medulloblastoma treatment has been determined by the amount of leftover disease present after surgery, also known as clinical risk (standard vs. high risk). Recent studies have shown that medulloblastoma is made up of distinct molecular subgroups which respond differently to treatment. This suggests that clinical risk alone is not adequate to identify actual risk of recurrence. In order to address this, we will stratify medulloblastoma treatment in this phase II clinical trial based on both clinical risk (low, standard, intermediate, or high risk) and molecular subtype (WNT, SHH, or Non-WNT Non-SHH). This stratified clinical and molecular treatment approach will be used to evaluate the following:

• To find out if participants with low-risk WNT tumors can be treated with a lower dose of radiation to the brain and spine, and a lower dose of the chemotherapy drug cyclophosphamide while still achieving the same survival rate as past St. Jude studies with fewer side effects.
• To find out if adding targeted chemotherapy after standard chemotherapy will benefit participants with SHH positive tumors.
• To find out if adding new chemotherapy agents to the standard chemotherapy will improve the outcome for intermediate and high risk Non-WNT Non-SHH tumors.
• To define the cure rate for standard risk Non-WNT Non-SHH tumors treated with reduced dose cyclophosphamide and compare this to participants from the past St. Jude study.