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

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