Vismodegib in Treating Younger Patients With Recurrent or Refractory Medulloblastoma

PRIMARY OBJECTIVES: I. Estimate the efficacy of GDC-0449 (vismodegib) treatment for pediatric patients with recurrent or refractory medulloblastoma, as measured by the sustained objective response rates for patients without (stratum A) and with (stratum B) evidence of activation of Hedgehog (Hh) signaling pathway in their tumors. II. Characterize the pharmacokinetics (plasma) of GDC-0449 in children/adolescents with refractory medulloblastoma. III. To document pathologic and genomic methods to identify medulloblastomas with activation of the Hh signaling pathway. SECONDARY OBJECTIVES: I. Document and describe toxicities associated with GDC-0449 administered on a daily schedule. II. Estimate the duration of objective response and progression-free survival (PFS). III. Characterize the pharmacokinetics (cerebrospinal fluid) of GDC-0449 in children/adolescents with refractory medulloblastoma. OUTLINE: This is a multicenter study. Patients are stratified according to evidence of activation of Hedgehog signaling pathway in their tumors (without vs with vs unknown). Patients receive vismodegib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity. Plasma and cerebrospinal fluid samples are collected periodically for pharmacokinetic and other correlative studies. After completion of study treatment, patients are followed up every other month for up to 12 months.