A Leap from TACE to TACE Potentiated by Immune Response Modulation and Angiogenesis Inhibition for Patients with Intermediate-Stage Hepatocellular Carcinoma: LEAP-012 Phase 3 Randomized Control Trial Protocol

Transarterial chemoembolization (TACE) has been a standard treatment for intermediate-stage hepatocellular carcinoma (HCC) for two decades with established survival benefit when compared to best supportive care [1, 2]. Embolization leads to upregulation of angiogenic growth factors including vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), which may in turn lead to accelerated growth of tumors outside of the targeted liver regions [3]. Added benefit of multi-kinase inhibitor sorafenib and TACE for patients with intermediate-stage HCC has been evaluated by the phase II randomized controlled SPACE trial, which included 307 patients treated with drug-eluting bead TACE (DEB TACE) with doxorubicin in combination with either sorafenib 400 mg twice daily or placebo. The study demonstrated no improvement in the primary outcome of time to progression for patients receiving TACE and sorafenib [4]. As a result, TACE continues to be performed as a monotherapy in current practice. …