Background: Therapeutic options are limited for refractory/relapsed adult medulloblastoma with activation of sonic hedgehog pathway (SHH-MB). Inhibition of this pathway may offer an attractive therapy. Vismodegib suppresses SHH signaling by binding to and interfering with the SMO transmembrane receptor. We postulate that vismodegib together with chemotherapy may kill more tumor cells than chemotherapy alone by blocking cell proliferation at different molecular levels (vertical association strategy). Methods: MEVITEM is a multicenter, randomized (2:1 ratio), open-label, Phase I/II aiming to evaluate the safety and clinical activity of the association vismodegib (V: daily 150mg/d) + temozolomide (T: D-5: 150 mg/m² for Cycle 1 and 200 mg/m² for subsequent cycles) versus T alone in adult patients with recurrent/refractory SHH-MB. Main eligibility criteria are: histologically confirmed recurrent/refractory SHH-MB for which no known curative therapy exists, not previously treated with T, with evidence of measurable disease and documented activation of SHH pathway. Pathological review and SHH pathway analysis are performed centrally by IHC. This Phase I/II includes i) a safety run aiming to evaluate the safety of V+T and ii) a Phase II part aiming to evaluate the clinical activity of V+T measured by the 6-month non-progression rate. Patients enrolled in the safety run are included in the evaluation of the Phase II part. Considering that V+T would be uninteresting if 6-month non-progression rate ≤ 30% and promising if ≥ 55% and using Simon’s optimal two-stage design (type I error rate:5%, power:80%), a sample size of 25 evaluable patients is required for Arm V+T (including 9 in stage I). The sample size in Arm T alone is 13 patients. Considering the rarity of SHH-MB, the few therapeutic options and the promising results reported with V in SHH-MB: the Sponsor considered the enrolment of patients previously treated by T in a 3^rdindependent and parallel arm with V as single agent (Arm V). To date, 18 patients were enrolled (Arm V+T: 7, Arm T: 4, Arm V: 7), the Phase II part is ongoing. Clinical trial information: NCT02029001