SARC031: A Phase 2 Trial of Selumetinib and Sirolimus for Patients with Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumors (MPNST)

Combined mTOR and MEK inhibition, critical components of the RAS effector pathway underlying the pathogenesis of NF1-related tumors, caused regression in a malignant peripheral nerve sheath tumors (MPNST) transgenic mouse model. The primary objective of this multi-institutional open label Simon 2 stage phase 2 study of the MEK inhibitor selumetinib and the mTOR inhibitor sirolimus was to determine the clinical benefit rate in patients with unresectable/metastatic MPNST. Correlative studies evaluated patient-reported pain, immune signature in peripheral blood, and cell-free DNA (cfDNA). Patients >=12 years with histologically confirmed MPNST received selumetinib 50mg twice daily and sirolimus 4mg once daily after a cycle 1 day 1 loading dose of 12mg, in continuous 28-day cycles.... (for more see dbGaP study page.)