Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma

1. Patients must be newly diagnosed and have:
   1. Eligibility confirmed by rapid central pathology and molecular screening review on APEC14B1:
      1. Classical histologic type (non LC/A) WNT medulloblastoma
      2. Positive nuclear beta-catenin by immunohistochemistry (IHC)
      3. Positive for CTNNB1 mutation
      4. Negative for MYC and MYCN by fluorescence in situ hybridization (FISH)
2. Patient must have negative lumbar cerebrospinal fluid (CSF) cytology
   1. Note: CSF cytology for staging should be performed no sooner than 14 days post operatively to avoid false positive CSF; ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study; patients with positive CSF cytology obtained 0 to 14 days after surgery should have cytology repeated to determine eligibility and final CSF status; patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated; patients with negative CSF cytology from lumbar puncture obtained prior to surgery do not need cytology repeated post-operatively
3. Patients must have eligibility confirmed by Rapid Central Imaging Review on APEC14B1; patients must have =< 1.5 cm^2 maximal cross-sectional area of residual tumor; whole brain magnetic resonance imaging (MRI) with and without gadolinium and spine MRI with gadolinium must be performed
4. Patients must be enrolled, and protocol therapy must be projected to begin, no later than 36 days after definitive diagnostic surgery (day 0)
5. Peripheral absolute neutrophil count (ANC) >= 1000/uL
6. Platelet count >= 100,000/uL (transfusion independent)
7. Hemoglobin >= 10.0 g/dL (may receive red blood cell [RBC] transfusions)
8. Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
   1. 3 to < 6 years of age: maximum (max) serum creatinine 0.8 mg/dL (males and females)
   2. 6 to < 10 years of age: max serum creatinine 1 mg/dL (males and females)
   3. 10 to < 13 years of age: max serum creatinine 1.2 mg/dL (males and females)
   4. 13 to < 16 years of age: max serum creatinine 1.5 md/dL (males) and 1.4 md/dL (females)
   5. >= 16 years of age: max serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL (females)
      1. The threshold creatinine values were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC)
9. Total or direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
10. Serum glutamate pyruvate (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (3x ULN); for the purpose of this study, the ULN for SGPT is 45 U/L
11. Central nervous system function defined as:
    1. Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
    2. Patients must not be in status epilepticus, a coma or on assisted ventilation at the time of study enrollment
12. Patients must have receptive and expressive language skills in English, French, or Spanish to complete the QoL and neurocognitive assessments; if a patient meets these criteria but the parent/guardian speaks a language other than English, French, or Spanish, the patient may still be enrolled and tested, and the parent-report measures should be omitted
13. All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
14. All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

For the most up-to-date list of criteria, please visit clinicaltrials.gov.

1. Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible; patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible
2. Patients must not have received any prior radiation therapy or chemotherapy (tumor-directed therapy) other than surgical intervention and/or corticosteroids
3. Pregnancy and Breast Feeding
   1. Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies
   2. Lactating females are not eligible unless they have agreed not to breastfeed their infants
   3. Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
   4. Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
4. Patients with a history of moderate to profound intellectual disability (i.e., intelligence quotient [Q)]=< 55) are not eligible for enrollment; PLEASE NOTE: Children with a prior history of attention deficit hyperactivity disorder (ADHD) or a specific learning disability (e.g., dyslexia) are eligible for this study

For the most up-to-date list of criteria, please visit clinicaltrials.gov.