Clinical Trials

INCLUSION CRITERIA:

• Medulloblastoma or medulloblastoma variants including posterior fossa PNET as documented by an institutional pathologist.
• Participant's age meets one of the following:
  • 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
  • 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.

EXCLUSION CRITERIA:

• 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.
• 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:
  • Participants must be Stratum S (SHH);
  • Participants must be skeletally mature defined as females with a bone age ≥ 15 years and males with a bone age ≥ 17 years;
  • Must be able to swallow pills - BSA must be >0.67 and <2.5 m2;
  • 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;
  • 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.
• Participants in the exercise intervention portion of the study must meet all criteria below: 
  • Must be ≥ 5 years and < 22 years at the time of enrollment;
  • Must have no congenital heart disease;
  • 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:
  • Completed protocol-directed radiation therapy;
  • ≥5 years at the time of remediation intervention consent;
  • English as primary language and training aide who speaks English available to participate in required sessions;
  • 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).