RESORCE: An ongoing randomized, double-blind, phase III trial of regorafenib (REG) in patients with hepatocellular carcinoma (HCC) progressing on sorafenib (SOR).

TPS4156^ Background: No standard treatment options are available for patients with HCC that has progressed despite SOR treatment. The oral multikinase inhibitor REG has been shown to have an acceptable safety profile and evidence of antitumor activity in patients with SOR-pretreated HCC (Bruix et al. Eur J Cancer 2013): disease control was achieved in 26/36 patients (72%), and median time to progression (TTP) was 4.3 months; median overall survival (OS) was 13.8 months. On the basis of these results, a phase III trial was designed. Methods: This randomized, double-blind, placebo (Pbo)-controlled, multinational study (ClinicalTrials.gov identifier NCT01774344) will compare the efficacy and tolerability of REG vs Pbo in adults with HCC that has progressed on SOR. Inclusion criteria include Barcelona Clinic Liver Cancer stage B or C disease that cannot benefit from established treatments, Child–Pugh Class A liver function, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. Patients discontinuing SOR >10 weeks before study entry or who received other previous systemic therapy for HCC will be excluded. Patients are randomized 2:1 to receive REG 160 mg or Pbo once daily for weeks 1–3 of each 4-week cycle; all patients also receive best supportive care. Treatment continues until disease progression, death, intolerable toxicity, or patient/investigator decision to stop. Doses of study drug may be delayed or reduced to manage clinically significant drug-related toxicities. The primary endpoint is OS; secondary endpoints are TTP, progression-free survival, objective tumor response, disease control, and safety. Analysis will be according to randomized group, stratified by geographic region (Asia vs rest of world), ECOG PS (0 vs 1), alfa-fetoprotein level (<400 vs ≥400 ng/ml), extrahepatic disease (yes vs no), and macrovascular invasion (yes vs no). In addition, blood, plasma, and archival tissue will be assessed for pharmacokinetic and biomarker analyses, and health-related quality of life will be measured. As of February 2014, 137 out of the planned 530 patients have been randomized. Clinical trial information: NCT01774344.