Risk-Directed Therapy for Medulloblastoma
What You Need to Know Before You Apply
What is the purpose of this trial?
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 indeterminableParticipants 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)
Who Is on the Research Team?
Amar Gajjar, MD
Principal Investigator
St. Jude Children's Research Hospital
Giles Robinson, MD
Principal Investigator
St. Jude Children's Research Hospital
Are You a Good Fit for This Trial?
This trial is for individuals aged 3-22 with newly diagnosed medulloblastoma, or those up to age 40 with SHH subtype. They must have had surgery within the last 36 days and not received prior brain tumor treatments. Good performance status is required, and women of childbearing potential must not be pregnant.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Surgery
Participants undergo surgery to remove as much of the primary tumor as safely possible
Radiation Therapy
Participants receive craniospinal irradiation with a boost to the primary tumor site, 5 days a week for 6 weeks
Chemotherapy
Participants receive adjuvant chemotherapy with cisplatin, vincristine, and cyclophosphamide for 4 cycles, with additional cycles for certain strata
Maintenance Therapy
Participants in certain strata receive maintenance therapy with vismodegib for 12 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- Cisplatin
- Craniospinal Irradiation with boost to the primary tumor site
- Cyclophosphamide
- Vincristine
- Vismodegib
Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:
- Testicular cancer
- Ovarian cancer
- Cervical cancer
- Bladder cancer
- Head and neck cancer
- Esophageal cancer
- Lung cancer
- Mesothelioma
- Brain tumors
- Neuroblastoma
- Testicular cancer
- Ovarian cancer
- Cervical cancer
- Bladder cancer
- Head and neck cancer
- Esophageal cancer
- Lung cancer
- Mesothelioma
- Brain tumors
- Neuroblastoma
- Testicular cancer
- Ovarian cancer
- Cervical cancer
- Bladder cancer
- Head and neck cancer
- Esophageal cancer
- Lung cancer
- Mesothelioma
- Brain tumors
- Neuroblastoma
- Testicular cancer
- Ovarian cancer
- Cervical cancer
- Bladder cancer
- Head and neck cancer
- Esophageal cancer
- Lung cancer
- Mesothelioma
- Brain tumors
- Neuroblastoma
Find a Clinic Near You
Who Is Running the Clinical Trial?
St. Jude Children's Research Hospital
Lead Sponsor
Genentech, Inc.
Industry Sponsor
Ashley Magargee
Genentech, Inc.
Chief Executive Officer since 2024
MBA from Harvard University, BA from Princeton University
Levi Garraway
Genentech, Inc.
Chief Medical Officer since 2021
MD, PhD
National Cancer Institute (NCI)
Collaborator