A blanket protocol to study oral regorafenib in patients with refractory liposarcoma, osteogenic

sarcoma, and Ewing/Ewing-like sarcoma

Coordinating Investigator:

Robert Maki, MD, PhDMount Sinai Medical Center

New York, NY

SARC024

SARC024

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

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 3rd line therapy in metastatic GIST

Regorafenib might be beneficial for other types of sarcoma

SARC024Cohort

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

Off substudy

Monthly imaging; Crossover

at progression

1:1

1:1

B

C Regorafenib; single stage substudy

Riedel

Ryan

Attia

Monthly imaging; Crossover

at progression

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!

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

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

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

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