Sorafenib and LBH589 in Hepatocellular Carcinoma (HCC)
Status:
Terminated
Trial end date:
2010-12-01
Target enrollment:
Participant gender:
Summary
Histone deacetylase inhibitors (HDACi) like LBH589 have recently been established as novel
potent anti-cancer agents for solid and hematologic malignancies. Several pre-clinical
reports have shown a good anti-tumoral activity of different HDACi on human or murine HCC
models. These compounds, e.g. Trichostatin A, SAHA, MS-275 and others, have been shown to
induce apoptosis in HCC cells and to inhibit growth of HCC by inhibiting proliferation and
tumor-related angiogenesis in vivo. Furthermore, HDACi sensitize HCC in a synergistic manner
to other forms of cytotoxic stimulation, e.g. by conventional chemotherapeutic drugs or
TRAIL-mediated apoptosis. It has also been shown that the combination of HDACi with various
kinase inhibitors like sorafenib, erlotinib or others, promotes the anti-tumor efficacy of
single agents.
Based on the investigators' own previous experiences with different HDACi and LBH589 in
preclinical HCC models, a strong anti-proliferative and pro-apoptotic as well as an
anti-angiogenic effect will be expected by combining LBH589 with an existing sorafenib
treatment. It is assumed that this combination will prolong overall survival and
time-to-progression with lowered adverse effects in HCC patients.
Phase:
Phase 1
Details
Lead Sponsor:
University of Erlangen-Nürnberg University of Erlangen-Nürnberg Medical School