A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma
Status:
Recruiting
Trial end date:
2026-12-01
Target enrollment:
Participant gender:
Summary
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.
All participants on this study will have surgery to remove as much of the primary tumor as
safely possible, radiation therapy, and chemotherapy. The amount of radiation therapy and
type of chemotherapy received will be determined by the participant's treatment stratum.
Treatment stratum assignment will be based on the tumor's molecular subgroup assignment and
clinical risk.
The participant will be assigned to one of three medulloblastoma subgroups determined by
analysis of the tumor tissue for tumor biomarkers:
- WNT (Strata W): positive for WNT biomarkers
- SHH (Strata S): positive for SHH biomarkers
- Non-WNT Non-SHH, Failed, or Indeterminate (Strata N): negative for WNT and SHH
biomarkers or results are indeterminable
Participants will then be assigned to a clinical risk group (low, standard, intermediate, or
high) based on assessment of:
- How much tumor is left after surgery
- If the cancer has spread to other sites outside the brain [i.e., to the spinal cord or
within the fluid surrounding the spinal cord, called cerebrospinal fluid (CSF)]
- The appearance of the tumor cells under the microscope
- Whether or not there are chromosomal abnormalities in the tumor, and if present, what
type (also called cytogenetics analysis)