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A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma
Sponsor: St. Jude Children's Research Hospital
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)
Key Details
Gender
All
Age Range
3 Years - 39 Years
Study Type
INTERVENTIONAL
Enrollment
660
Start Date
2013-06-23
Completion Date
2031-10-13
Last Updated
2025-11-13
Healthy Volunteers
No
Conditions
Interventions
Craniospinal Irradiation with boost to the primary tumor site
All participants will undergo craniospinal irradiation (CSI) with boost to the primary tumor site. The dose given is based on the molecular and risk group as noted in the arm descriptions. The type of radiation used includes conformal radiation therapy (photons) or intensity modulated radiation therapy (IMRT) or proton beam therapy.
Cyclophosphamide
Route of Administration (ROA): Intravenously (IV)
Cisplatin
ROA: IV
Vincristine
ROA: IV
Vismodegib
ROA: Orally (PO)
Pemetrexed
ROA: IV
Gemcitabine
ROA: IV
Aerobic Training
Neurocognitive Remediation
Locations (23)
Lucille Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, United States
Rady Children's Hospital
San Diego, California, United States
Yale University
New Haven, Connecticut, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
University of Florida
Gainesville, Florida, United States
Arnold Palmer Hospital for Children
Orlando, Florida, United States
Children's Hospital and Clinics of Minnesota
Minneapolis, Minnesota, United States
Duke Children's Hospital and Health Center
Durham, North Carolina, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Texas Children's Cancer Center
Houston, Texas, United States
Sydney Children's Hospital
Randwick, New South Wales, Australia
Children's Hospital at Westmead
Westmead, New South Wales, Australia
Queensland Children's Hospital
Brisbane, Queensland, Australia
Royal Children's Hospital, Melbourne
Melbourne, Victoria, Australia
Perth Children's Hospital
Perth, Western Australia, Australia
Alberta Children's Hospital
Calgary, Alberta, Canada
The Hospital for Sick Children
Toronto, Ontario, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada
Starship Children's Hospital
Auckland, New Zealand