A Randomized, Double-Blinded, Placebo- Controlled, Multi-Institutional, Cross-Over Phase II.5 Study of Saracatinib, a Selective Src Kinase Inhibitor, in Patients with Recurrent Osteosarcoma Localized to the Lung Principal Investigator: Melinda Merchant, MD, PhD Pediatric Oncology Branch National Cancer Institute, National Institutes of Health SARC012

 SARC  Sponsor and coordinating center  AstraZeneca  Supporter

SARC012  Background  Phase II.5 study of saracatinib in recurrent osteosarcoma localized to the lung  2012 protocol amended to allow cross-over if progression on placebo  June 2013 IDMC recommended study remain open to interim analysis

SARC012 Resection of all remaining nodules, verification of recurrent osteosarcoma Randomized to receive saracatinib or placebo continuous (364 days/13 cycles) Thoracic CT Wk 3-4, 6-8; then every 3 months Complete 13 cycles Study Follow up Recur in lung while on study Unblinding  Patients on placebo may undergo another resection, and if fully resected, will be given option to receive saracatinib for 13 cycles.

SARC012 Study Sites  Sites Open for Enrollment  National Cancer Institute  Stanford  University of Alabama  University of Michigan  UCLA  Sarcoma Oncology Ctr  U of Wash –Seattle CC  St. Jude’s  Johns Hopkins  University of Iowa  Cincinnati Children’s Hospital  Dana Farber  Dana Farber Partners CC  University of Miami  University of Florida  Children’s Hospital LA  USC

Study Status  Enrollment  n= 43  Randomized pts  n= 36  On study treatment  n= 5  Off study  n= 22  In follow-up  n= 7  Cross over  n= 2  Goal for Interim Analysis  n= 40 Randomized patients