Phase 2 study of the mTOR inhibitor RAD001 (everolimus) in combination with bevacizumab (avastin) in patients with sporadic and neurofibromatosis type 1 (NF1) related refractory malignant peripheral nerve sheath tumors Principal Investigator: Brigitte Widemann, MD National Cancer Institute, National Institutes of Health SARC016

 SARC  Sponsor and coordinating center  DoD  Grant supporting clinical trial  Novartis  Providing everolimus  Genetech  Providing bevacizumab

SARC016  Background  NF1 activation results in aberrant activation mTOR  Sirolimus halts tumor growth and prolongs survival in a genetically engineered NF1 mouse model of MPNST  VEGF expression is increased in MPNST and correlates with poor outcome

Patients with NF1 related or sporadic refractory MPNST N=25 patients 28 day cycles of everolimus (daily dosing) + bevacizumab (day 1 and 14) 2 stage design: If > 1 of 15 pt respond accrual will continue to a total of 25 patients Ongoing tumor assessment imaging every 2 cycles until disease progression or unacceptable toxicity for a maximum of 2 years SARC016 Primary objectives: Clinical benefit rate (CR, PR, SD at ≥ 4 months, WHO) Toxicity and safety of RAD001 and bevacizumab

SARC016 Participation  Sites open to enrollment  National Cancer Institute  Pennsylvania Oncology  Lurie Children’s Hospital of Chicago  University of Michigan  Washington University, St. Louis  Children’s National Medical Center  Johns Hopkins  University of Iowa  Cincinnati Children’s Hospital  Massachusetts General Hospital and Dana Farber  Sites pending  University of Alabama at Birmingham  Children’s Hospital of Philadelphia

Study Status  Current Enrollment  n= 9  On study treatment  n= 2  Off study  n= 7