Background: Despite therapeutic advances, patient outcomes in mRMS and mNRSTS remain poor. The phase I study (Glade-Bender et al., J Clin Oncol. 2008) indicated that Bv is well tolerated in children with refractory solid tumors and yielded pharmacokinetic (PK) data that support further studies of Bv in childhood cancer. Reports of Bv used in children with solid tumors showed safety profiles consistent with data from adults. Methods: In this phase II trial, 150 patients aged 6 months to 18 years who present with mRMS or mNRSTS are randomized to receive 18 months of standard combined modality therapy as per EpSSG guidelines, either alone or with Bv. Treatment consists of 2 phases: induction therapy [9 three-weekly cycles including 4 cycles of IVADo (ifosfamide, vincristine, actinomycin D, and doxorubicin), followed by 5 cycles of IVA (i.e., without doxorubicin)] and maintenance therapy (12 four-weekly cycles of vinorelbine and cyclophosphamide). Local therapy is considered after the 6th induction cycle. Primary endpoint is event-free survival (EFS). PK sampling is performed on all patients randomized to the experimental arm during the first 4 cycles of induction. After the primary efficacy and safety analysis, all patients who have not met the primary endpoint are followed for at least 47 months for survival and long-term effects of treatment. The study enrolled 75 patients between July 2008 and January 2012; 37 patients discontinued study treatment (including 17 patients who died, all due to disease progression) and 9 patients have completed study treatment.