Vismodegib in Treating Patients With Recurrent or Refractory Medulloblastoma

PRIMARY OBJECTIVES: I. To estimate the efficacy of GDC-0449 (vismodegib) treatment for adult patients with recurrent or refractory medulloblastoma, as measured by the objective response rates for patients without (Stratum A) and with (Stratum B) evidence of activation of Sonic Hedgehog (SHH) signaling pathway tumors. SECONDARY OBJECTIVES: I. To assess the safety and tolerability of GDC-0449 administered on a once daily schedule. II. To estimate the duration of objective response and progression-free survival (PFS). III. To characterize the pharmacokinetics (plasma and cerebrospinal fluid) of GDC-0449 in adults with refractory medulloblastoma. IV. To document pathologic and genomic methods to identify CNS tumors with activation of the PTCH/SHH pathway. V. To describe the objective responses observed in patients whose pathologic assessment of tumor result in unknown (Stratum C) evidence of activation of Sonic Hedgehog (SHH) signaling pathway tumors. OUTLINE: This is a multicenter study. Patients are stratified according to PTCH/Sonic Hedgehog signaling pathway activation (inactivated vs activated vs unknown). Patients receive vismodegib orally (PO) once daily on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for up to 12 months.