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

INCLUSION CRITERIA

1. Medulloblastoma or medulloblastoma variants including posterior fossa PNET as documented by an institutional pathologist.
2. 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).
3. No previous radiotherapy, chemotherapy or other brain tumor directed therapy other than corticosteroid therapy and surgery.
4. 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).
5. Adequate performance status: children < 10-Lansky Score ≥ 30; children ≥ 10-Karnofsky ≥ 30 (except for posterior fossa syndrome).
6. 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.

EXCLUSION CRITERIA

1. 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.
2. 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:

1. Participants must be Stratum S (SHH)
2. Participants must be skeletally mature defined as females with a bone age ≥ 15 years and males with a bone age ≥ 17 years.
3. Must be able to swallow pills
4. BSA must be >0.67 and <2.5 m2
5. 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
6. ANC ≥ 1000/mm^3 (after G-CSF discontinued)
7. Platelets ≥ 50,000/mm^3 (without support)
8. Hgb ≥ 8 g/dL (with or without transfusion support)
9. Serum creatinine ≤ 1.5 mg/dL
10. Total bilirubin ≤ 1.5X the institutional ULN
11. SGPT (ALT) ≤ 2.5X the institutional ULN
12. SGOT (AST) ≤ 2.5X the institutional ULN
13. Alkaline Phosphatase ≤ 1.5X the institutional ULN
14. Serum albumin ≥ 2.5 g/dL

Participants in the exercise intervention portion of the study must meet all criteria below:

1. Must be ≥ 5 years and < 22 years at the time of enrollment
2. Must have no congenital heart disease
3. 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:

1. Completed protocol-directed radiation therapy
2. ≥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
3. English as primary language and training aide who speaks English available to participate in required sessions
4. 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
5. 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)