A Study of Sorafenib in Patients With Chemonaive Metastatic Uveal Melanoma
Status:
Unknown status
Trial end date:
2017-06-01
Target enrollment:
Participant gender:
Summary
Uveal melanoma is the most common primary intra-ocular malignancy in adults with an incidence
of 0.6 - 0.7 per 100,000 per year.
Prognosis of metastatic uveal melanoma is poor. In retrospective analyses a median survival
time after detection of metastases of 5 months (Flaherty et al, 1998) and 7 months (Kath et
al, 1993) was reported. For patients receiving no treatment reported median survival was 2.0
months compared with 5.2 months for those receiving treatment for metastases (Gragoudas et
al, 1991).
Up to now there is no established treatment of metastatic uveal melanoma. Some therapeutic
approaches with locoregional treatment or systemic chemotherapy have been undertaken:
In case of metastatic disease which is confined to the liver in about 85% of patients with
uveal melanoma surgical resection led to a median survival of 14 months (Mariani et al, 2009)
or 19 months and a 5-year survival rate of 22% in a selected patient population (Adam et al,
2006).
As locoregional treatment option treatment with fotemustine via direct intra-arterial hepatic
infusion was investigated and led to a median survival of 15 months (Peters et al, 2006).
This was not a randomized trial, but a report on 101 consecutive treated patients. Additional
debulking surgery was performed whenever feasible.
A randomized phase III trial comparing intra-arterial hepatic fotemustine administration with
intravenous systemic fotemustine and overall survival as primary endpoint is still ongoing
(EORTC 18021).
Thus, no systemic chemotherapy is approved for metastatic uveal melanoma. Although no
specific genes have been linked to the pathogenesis of uveal melanoma, preclinical studies
suggest potential benefit of inhibitors of Bcl-2, ubiquitin-proteasome, histone deactylase,
mitogen-activated protein kinase and phosphatidylinositol-3-kinase-AKT pathways, and receptor
tyrosine kinases.
Thus, sorafenib as inhibitor of b-Raf and Raf-1 (c-Raf or c-Raf-1), pro-angiogenic vascular
endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor
(PDGFR) may potentially lead to a benefit for patients with metastatic uveal melanoma in
terms of disease control and prolongation of survival.