1. A blanket protocol to study oral regorafenib in patients with refractory liposarcoma, osteogenic sarcoma, and Ewing/Ewing-like sarcoma Coordinating Investigator: Robert Maki, MD, PhD Mount Sinai Medical Center New York, NY SARC024

2.  Co-principal investigators  Chris Ryan, MD  Osteosarcoma cohort  Richard Riedel, MD  Liposarcoma cohort  Steven Attia, MD  Ewing/Ewing-like cohort  SARC  Sponsor and coordinating center  Bayer  Supporter

3. Background  Pazopanib is approved for advanced/metastatic STS other than GIST, liposarcoma  Sorafenib has minor activity in STS in a phase II trial  An Italian report indicates activity of sorafenib in osteosarcoma  Regorafenib is closely related to sorafenib, and is approved 3 rd line therapy in metastatic GIST  Regorafenib might be beneficial for other types of sarcoma

4. SARC024 Cohort A Liposarcoma (all subtypes except pure well diffs) Osteogenic sarcoma (bone or soft tissue) Ewing/Ewing-like sarcoma (bone or soft tissue) R R Regorafenib Placebo Regorafenib Placebo Off substudy Monthly imaging; Crossover at progression 1:1 B C Regorafenib; single stage substudy Riedel Ryan Attia Monthly imaging; Crossover at progression

5. SARC024  Cohort A and Cohort B:  Randomized, double blinded, placebo-controlled, phase II design  n=48 total patients per substudy  Cohort C:  Single stage, single arm phase II design, n=30  Rx (28 day cycle): regorafenib (± vs placebo), 160 mg oral daily, 3 weeks on, 1 week off  Watch out for toxicity!

6. Primary Objectives  Cohort A and Cohort B:  Compare the progression-free survival (PFS) of eligible subjects treated with regorafenib vs. placebo  Cohort C:  To estimate the RECIST 1.1 PFS rate of eligible subjects treated with regorafenib at 8 and 16 weeks

7. Inclusion Criteria  Patients ≥ 18 years old (sorry)  Advanced/metastatic liposarcoma, osteogenic sarcoma, or Ewing/Ewing-like sarcoma of soft tissue or bone histologically or cytologically confirmed  At least one prior line of systemic therapy  WHO performance status of 0-2

8. Inclusion Criteria  Patient must be able to swallow medication  Adequate organ function within 14 days of registration  Evidence of disease progression (as defined by RECIST 1.1) within 6 months of registration

9. Study Status  Contracting  In process  Anticipated completion November/December 2013  Sites  In process of querying sites on interest and capabilities  Activation  Late 2013 / Early 2014