A Multicenter Phase II Study of Sorafenib (BAY43-9006) in Non-GIST Sarcomas
I. The primary endpoint is the response rate (CR+PR) for each stratum of sarcoma patients
treated with sorafenib as defined by RECIST.
I. Progression-free survival (defined as CR + PR + SD, assessed at 3 months or 6 months).
II. Overall survival. III. Pharmacokinetics of sorafenib in this patient population (all
sites will participate).
IV. Frequency of B-raf mutations in the patients' sarcomas treated as part of this study and
correlation with response or resistance to sorafenib (all sites will participate).
V. Ras-raf kinase pathway activation in pre-treatment existing tumor specimens (paraffin
section immunohistochemistry; all sites will participate).
VI. At MSKCC only: Pre and post treatment specimen changes in downstream events of ras
signaling, specifically inhibition of ERK phosphorylation. Only patients with angiosarcoma
and MPNST will undergo biopsy (up to 10 patients).
VII. At MSKCC only: Circulating Endothelial Cells (CECs), VE-cadherin levels, and soluble
protein levels (VEGF, bFGF, endostatin) as a measures of angiogenesis before and after
starting sorafenib therapy.
OUTLINE: This is an open-label, non-randomized, multicenter study. Patients are stratified
according to sarcoma histology (angiosarcoma vs malignant peripheral nerve sheath tumor vs
leiomyosarcoma [closed to accrual as of 11/29/06] vs high-grade undifferentiated pleomorphic
sarcoma [i.e., malignant fibrous histiocytoma (including myxofibrosarcoma)(closed to accrual
as of 11/29/06)] vs synovial sarcoma (closed to accrual as of 11/29/06) vs all other types
Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in
the absence of disease progression or unacceptable toxicity.
After completion of study, patients are followed at 4 weeks.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall response rate measured by complete response (CR) rate and partial response (PR) rate as determined by RECIST
A 5% response rate is considered not promising, a 20% response rate is considered promising. For each stratum, the response rate will be estimated and a confidence interval will be constructed.
Up to 4 weeks
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|