A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma

Prior treatment

• Research participants with other clinically significant medical disorders that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results history.
  • Participants in the Stratum S maintenance chemotherapy portion of the study must meet the criteria below prior to start of vismodegib therapy:
• Male and female participants of reproductive potential must agree to effective contraception during and after study treatment. See Appendices I and II for further guidance for participants receiving vismodegib
• Completed protocol-directed radiation therapy

Other illness

• Must have no congenital heart disease
• No significant cognitive impairment operationalized as either an IQ \< 70 for children with St. Jude SJMB12 study baseline testing or based on clinician judgment baseline IQ missing
• No major sensory or motor impairment that would preclude valid cognitive testing (e.g., unresolved posterior fossa syndrome, blindness, poorly controlled seizures/photosensitive epilepsy, psychosis) or a major psychological condition that would preclude completion of the intervention (e.g., significant oppositionality, autism spectrum disorder, severe anxiety or depressive symptoms)

Lab values

• ANC ≥ 1000/mm\^3 (after G-CSF discontinued)
• Platelets ≥ 50,000/mm\^3 (without support)
• Hgb ≥ 8 g/dL (with or without transfusion support)
• Serum creatinine ≤ 1.5 mg/dL
• Total bilirubin ≤ 1.5X the institutional ULN
• SGPT (ALT) ≤ 2.5X the institutional ULN
• SGOT (AST) ≤ 2.5X the institutional ULN
• Alkaline Phosphatase ≤ 1.5X the institutional ULN
• Serum albumin ≥ 2.5 g/dL
  • Participants in the exercise intervention portion of the study must meet all criteria below:

Age

• Participants must be skeletally mature defined as females with a bone age ≥ 15 years and males with a bone age ≥ 17 years.
• Must be ≥ 5 years and \< 22 years at the time of enrollment
• ≥5 years at the time of remediation intervention consent or age is greater than or equal to 22 years and less than 40 years and patient has SHH medulloblastoma

Other

• CNS embryonal tumor other than medulloblastoma or PNET in the posterior fossa, for example, patients with diagnosis of Atypical Teratoid / Rhabdoid Tumor (ATRT), supratentorial PNET, pineoblastoma, ependymoblastoma, ETANTR are excluded.
• Participants must be Stratum S (SHH)
• Must be able to swallow pills
• BSA must be \>0.67 and \<2.5 m2
• Must be capable of performing the exercise intervention at the time of baseline assessment as determined by the treating physician.
  • Participants in the cognitive remediation intervention portion of the study must meet all criteria below:
• English as primary language and training aide who speaks English available to participate in required sessions

• Medulloblastoma or medulloblastoma variants including posterior fossa PNET as documented by an institutional pathologist.
• Participant's age meets one of the following: (1) Age greater than or equal to 3 years and less than 22 years of age at the time of diagnosis (may enroll on Strata W, S or N), OR (2) age is greater than or equal to 22 years and less than 40 years AND patient has SHH medulloblastoma (must enroll on Stratum S).
• No previous radiotherapy, chemotherapy or other brain tumor directed therapy other than corticosteroid therapy and surgery.
• Patients must begin treatment as outlined in the protocol within 36 days of definitive surgery (day of surgery is day 0; definitive surgery includes second surgeries to resect residual tumor).
• Adequate performance status: children \< 10-Lansky Score ≥ 30; children ≥ 10-Karnofsky ≥ 30 (except for posterior fossa syndrome).
• Females of child-bearing potential cannot be pregnant or breast-feeding. Female participants \> 10 years of age or post-menarche must have a negative serum or urine pregnancy test prior to enrollment.
• Biological parent(s) of participant (child) enrolling on this protocol. These parents will be assigned to cohort P. The exclusion criteria below do not apply to this cohort.