Multicentric prospective study of validation of angiogenesis polymorphisms in HCC patients treated with sorafenib. INNOVATE study

Background

Preclinical data suggested that significant HCC growth is dependent on angiogenesis.In the ALICE-2 we study patients (PT) receiving sorafenib(S) for HIF-1α,VEGF-A and VEGF-C SNPs.At multivariate analysis rs12434438 of HIF-1α,rs2010963 of VEGF-A and rs4604006 of VEGF-C have been confirmed as independent factors for PFS and OS. At the combined analysis of significant SNPs the presence of 2 favourable alleles of VEGF compared to only 1 or to none favourable alleles, identifies three populations with different PFS(respectively:10.8 vs. 5.6 vs. 3.7 months,p 

Trial design

This is a prospective non pharmacological study. The study population consisted of PT with advanced-stage HCC and PT not eligible for locoregional treatments or liver transplantation.The primary aim of the study is to validated the prognostic or predictive role of eNOS,Ang2,HIF-1, VEGF and VEGFR SNPs in relation to clinical outcome of PT treated with S. The secondary aim of the study is to verify the prognostic value of the basal level of ldh, blood pressure, plasma level of Ang2 and plasma level of VEGF in relation to clinical outcome (progression-free survival and overall survival) of patients treated with S. The study was planned to have a 90% power at the 5% significance level (two-sided) to detect a 42% relative reduction in the progression rate (absolute increase in PFS of 2.5 months). Assuming a 24-month accrual period and a 12-month follow-up, 160 patients were required.

Clinical trial identification

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Legal entity responsible for the study

Andrea Casadei Gardini

Funding

IRST-IRCCS

Disclosure

All authors have declared no conflicts of interest.