Vismodegib in Treating Younger Patients With Recurrent or Refractory Medulloblastoma

Inclusion Criteria

• Patients with a histologically confirmed diagnosis of medulloblastoma that is recurrent, progressive, or refractory to standard therapy and for which there is no known curative therapy
• Patient must have adequate archival formalin fixed, paraffin embedded (FFPE) primary tumor material for biology studies; specifically, adequate archival FFPE tumor material is either:
• An FFPE block, preferably in which tumor occupies an area of at least 10x10 mm if available, and is free of surgical or processing artifacts; tumor in the submitted FFPE block must not have been obtained from the CUSA trap OR
• Preferably15x5µm sections if available from an FFPE tissue block conforming to the above criteria AND
• Tissue submission must be accompanied by a copy of the pathology report
• Patients must have bi-dimensionally measureable disease in the brain or spinal cord defined as at least one lesion that can be accurately measured in at least 2 planes in order to be eligible for this study
• Patients must have a body surface area (BSA) of >= 0.67m^2 and at most 2.5m^2
• Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration; this is to be documented in the database
• Karnofsky performance status of >= 50% in patients > 16 years, or Lansky performance status of >= 50% in patients >= 3 yrs and = = 3 months prior to study entry for craniospinal irradiation; >= 8 weeks for local irradiation to primary tumor; >= 2 weeks prior to study entry for focal irradiation for symptomatic metastatic sites
• Off all colony stimulating factors > 1 week prior to study entry (granulocyte colony stimulating factor [GCSF], granulocyte macrophage colony stimulating factor [GM CSF], erythropoietin)
• Prior therapy will include primary therapy (including radiation therapy and chemotherapy) and a maximum of 2 additional salvage therapies; patients can enroll on the protocol after failure on primary therapy
• Absolute neutrophil count (ANC) >= 1000 µL
• Platelet count >= 50,000/uL (transfusion independent)
• Hemoglobin >= 8.0 gm/dL (may receive red blood cell [RBC] transfusions)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70ml/min/1.73 m^2 or a serum creatinine = = 2.5 g/dL
• Patient must have recovered from the significant acute toxicities of all prior therapy before entering this study and meet all other eligibility criteria specified in the Inclusion and Exclusion Criteria
• Pregnancy should be avoided for 12 months after the last dose of GDC-0449 for females of child-bearing potential; female patients of childbearing potential must not be pregnant or breast-feeding; female patients of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to beginning treatment
• Women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) within 10-14 days and within 24 hours prior to the first dose of GDC-0449 (serum or urine); a pregnancy test (serum or urine) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study within the 24-hour period prior to the administration of GDC-0449; prior to dispensing GDC-0449, the investigator must confirm and document the patient's use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the of GDC-0449 to cause spontaneous abortion or birth defects; female patients are required to use two forms of acceptable contraception, including one barrier method during participation in the study and for the 12 months following the last dose; all patients should receive contraceptive counseling either by the investigator, or by an obstetrician (OB), gynecologist or other physician who is qualified in this area of expertise; if a woman of childbearing potential believes that her contraceptive method has fa