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

Inclusion Criteria:

• Patients must be greater than or equal to 3 years and less than 22 years of age atthe time of enrollment

• Patients must be newly diagnosed and have:

• Eligibility confirmed by rapid central pathology and molecular screening reviewon APEC14B1:

• Classical histologic type (non LC/A) WNT medulloblastoma

• Positive nuclear beta-catenin by immunohistochemistry (IHC)

• Positive for CTNNB1 mutation by Sanger sequencing

• Negative for MYC and MYCN by fluorescence in situ hybridization (FISH)

• Patient must have negative lumbar cerebrospinal fluid (CSF) cytology

• Note: CSF cytology for staging should be performed no sooner than 14 days postoperatively to avoid false positive CSF; ideally, CSF should be obtainedbetween day 14 and day 21 to allow for final staging status before enrollmentonto the study; patients with positive CSF cytology obtained 0 to 14 days aftersurgery should have cytology repeated to determine eligibility and final CSFstatus; patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated; patients with negative CSFcytology from lumbar puncture obtained prior to surgery do not need cytologyrepeated post-operatively

• Patients must have eligibility confirmed by Rapid Central Imaging Review onAPEC14B1; patients must have =< 1.5 cm^2 maximal cross-sectional area of residualtumor; whole brain magnetic resonance imaging (MRI) with and without gadolinium andspine MRI with gadolinium must be performed

• Patients must be enrolled, and protocol therapy must be projected to begin, no laterthan 36 days after definitive diagnostic surgery (day 0)

• Peripheral absolute neutrophil count (ANC) >= 1000/uL

• Platelet count >= 100,000/uL (transfusion independent)

• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

• 3 to < 6 years of age: maximum (max) serum creatinine 0.8 mg/dL (males andfemales)

• 6 to < 10 years of age: max serum creatinine 1 mg/dL (males and females)

• 10 to < 13 years of age: max serum creatinine 1.2 mg/dL (males and females)

• 13 to < 16 years of age: max serum creatinine 1.5 md/dL (males) and 1.4 md/dL (females)

• >= 16 years of age: max serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL (females)

• The threshold creatinine values were derived from the Schwartz formula forestimating GFR utilizing child length and stature data published by theCenters for Disease Control and Prevention (CDC)

• Total or direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and

• Serum glutamate pyruvate (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (3xULN); for the purpose of this study, the ULN for SGPT is 45 U/L

• Central nervous system function defined as:

• Patients with seizure disorder may be enrolled if on anticonvulsants and wellcontrolled

• Patients must not be in status epilepticus, a coma or on assisted ventilationat the time of study enrollment

• Patients must have receptive and expressive language skills in English, French, orSpanish to complete the QoL and neurocognitive assessments; if a patient meets thesecriteria but the parent/guardian speaks a language other than English, French, orSpanish, the patient may still be enrolled and tested, and the parent-reportmeasures should be omitted

• All patients and/or their parents or legal guardians must sign a written informedconsent; assent, when appropriate, will be obtained according to institutionalguidelines

• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

• Patients with metastatic disease by either MRI evaluation (brain and spine) orlumbar CSF cytology are not eligible; patients who are unable to undergo a lumbarpuncture for assessment of CSF cytology are ineligible

• Patients must not have received any prior radiation therapy or chemotherapy (tumor-directed therapy) other than surgical intervention and/or corticosteroids

• Pregnancy and Breast Feeding

• Female patients who are pregnant are ineligible due to risks of fetal andteratogenic adverse events as seen in animal/human studies

• Lactating females are not eligible unless they have agreed not to breastfeedtheir infants

• Female patients of childbearing potential are not eligible unless a negativepregnancy test result has been obtained

• Sexually active patients of reproductive potential are not eligible unless theyhave agreed to use an effective contraceptive method for the duration of theirstudy participation

• 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) ora specific learning disability (e.g., dyslexia) are eligible for this study.Children with posterior fossa syndrome (also known as cerebellar mutism) areeligible for this study