A Randomized Double-blind, Placebo-controlled Japanese Phase III Trial of ARQ 197 in Hepatocellular Carcinoma (HCC)

Inclusion criteria

• Informed consent form
• ≥20 years old
• Inoperable HCC which is not eligible for locoregional therapy
• Diagnosed as c-Met high in tumor sample
• Radiographic progression is confirmed during or after systemic chemotherapy including sorafenib, or those who are intolerance to the chemotherapy.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) is 0 or 1
• Child-Pugh Class A
• Having measurable target lesions which are defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1,
• Negative pregnancy test results
• Adequate organ function
• Life expectancy of at least 12 weeks

Exclusion criteria

• More than 2 prior systemic chemotherapy.
• Prior therapy of c-Met inhibitor (including antibody)
• Any systemic therapy within ≤2 weeks prior to the randomization
• Locoregional therapy within ≤4 weeks prior to randomization.
• Major surgery within ≤4 weeks prior to the randomization
• Concurrent cancer within ≤5 years prior to the randomization
• History of cardiac diseases
• Active clinically serious infections defined as ≥ Grade 3 according to Common Toxicity Criteria for Adverse Effects (CTCAE) 4.0
• Any psychological disorder affecting Informed Consent
• Diagnosis positive for anti-HIV antibody and/or anti-HTLV-1 antibody
• Blood or albumin transfusion within ≤14 days prior to the screening test
• Concurrent interferon therapy against Hepatitis B Virus (HBV)/ Hepatitis C Virus (HCV)
• Symptomatic brain metastases
• History of liver transplantation
• Inability to swallow oral medications
• Confirmed interstitial lung disease
• Pleural effusion and/or clinically significant ascites
• Pregnancy or breast-feeding
• Without consent to effective single or combined contraceptive methods