A Multicenter, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib (E7080) Versus Sorafenib in First-line Treatment of Participants With Unresectable Hepatocellular Carcinoma

• Participants must have confirmed diagnosis of unresectable HCC with any of the following criteria:
• Histologically or cytologically confirmed diagnosis of HCC.
• Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria, including cirrhosis of any etiology or with chronic hepatitis B or C infection criteria
• At least one measurable target lesion according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) meeting the following criteria:
• Hepatic lesion
• The lesion can be accurately measured in at least one dimension as >=1.0 centimeter (cm) (viable tumor for typical; and longest diameter for atypical), and
• The lesion is suitable for repeat measurement.
• Nonhepatic lesion
• Lymph node (LN) lesion that measures at least one dimension as >=1.5 cm in the short axis, except for porta hepatis LN that measures >=2.0 cm in the short axis.
• Non-nodal lesion that measures >=1.0 cm in the longest diameter Lesions previously treated with radiotherapy or locoregional therapy must show radiographic evidence of disease progression to be deemed a target lesion.
• Participants categorized to stage B (not applicable for transarterial chemoembolization [TACE]) or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system.
• Adequate bone marrow function, defined as:
• Absolute neutrophil count (ANC) >=1.5 X 10^9 per liter (/L)
• Hemoglobin (Hb) >=8.5 gram per deciliter (g/dL)
• Platelet count >=75 X 10^9/L.
• Adequate liver function, defined as:
• Albumin >=2.8 g/dL
• Bilirubin less than or equal to ( ) 40 milliliter per minute (mL/min) calculated per the Cockcroft and Gault formula.
• Adequate pancreatic function, defined as amylase and lipase 18 years as determined by country legislation) at the time of informed consent.
• Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity of 25 International Units Per Liter (IU/L) or equivalent units of BhCG).

A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.

• All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all with surgery at least 1 month before dosing).
• Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the participant must agree to use a double barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.
• Male participants must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation). No sperm donation is allowed during the study period and for 30 days after study drug di