Background: TACE is regarded as the standard of care for patients (pts) with intermediate stage HCC while sorafenib (S) is the current standard for advanced disease. TACE 2 was designed to determine whether TACE + S improves progression free survival (PFS) compared to TACE alone. Methods: Pts with HCC were randomised 1:1 to continuous S (400mg BD) or placebo (P). Inclusion criteria included unresectable, liver confined HCC, patent main portal vein, ECOG PS ≤ 1 and Child Pugh A liver score. Study drug was commenced at randomisation and TACE performed at 2-5 weeks using drug eluting beads (DEB) loaded with 150mg doxorubicin. Further TACE was performed according to radiological response and patient tolerance. Primary outcome measure was PFS. Secondary outcome measures included overall survival (OS) and toxicity. Target recruitment was 412 to detect a (Hazard Ratio) HR of 0.72 with 2-sided significance α = 0.05 and 85% power. Treatment HR in the intention to treat population was estimated by Cox survival model. A planned interim futility analysis was performed at 45% of trial events. Results: The interim futility analysis, performed July 2015, led to trial termination in December. At the interim analysis, 294 were randomised to S (n = 147) or P (n = 147) from 20 UK sites. Median age was 67 yrs and 169 (58%) were PS 0. In 229 (79%) cirrhotic pts, liver disease was: 54 (24%) HCV; 30 (13%) HBV; 99 (43%) alcohol; 86 (38%) other. Median follow-up was 15.2 months. Median PFS for the S and P group was 7.8 (95% CI 5.9, 10.0) and 7.7 (95% CI 5.9, 10.5) months; (HR) of 1.03 (95% CI 0.75, 1.42 p = 0.85). For the S and P groups: median OS was 18.8 (95% CI 12.3, 24.0) and 19.6 (95% CI 14.8, 24.0) months; there were 77 and 78 SAEs; 195 and 256 TACE procedures. Median duration of S and P was 5.9 and 7.7 months; median of patient average daily dose was 649mg and 800mg. Conclusions: The TACE 2 trial provides no evidence that addition of S to DEB TACE improves PFS or OS in European pts with intermediate HCC. Alternative systemic therapies need to be evaluated in combination with TACE to improve outcome for this patient population. Clinical trial information: ISRCTN93375053.