A Study of Ramucirumab (IMC-1121B) Drug Product (DP) and Best Supportive Care (BSC) Versus Placebo and BSC as 2nd-Line Treatment in Participants With Hepatocellular Carcinoma After 1st-Line Therapy With Sorafenib

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1

Child-Pugh score of \<7 (Child-Pugh Class A only)

Barcelona Clinic Liver Cancer (BCLC) Stage C or BCLC stage B not amenable to locoregional therapy or refractory to locoregional therapy

Diagnosis of HCC (excluding fibrolamellar carcinoma) in the absence of histologic or cytologic confirmation

There are either clinical, laboratory, or radiographic findings consistent with a diagnosis of liver cirrhosis

Has a liver mass measuring at least 2 centimeters (cm) with characteristic vascularization seen on either triphasic computed tomography (CT) scan or magnetic resonance imaging (MRI) with gadolinium

At least 1 measurable or evaluable lesion that is viable \[that is (i.e.), is vascularized\], and has not been previously treated with locoregional therapy. A lesion that has been previously treated will qualify as a measurable or evaluable lesion if there was demonstrable progression following locoregional therapy

Previously treated with sorafenib and has discontinued sorafenib treatment at least 14 days prior to randomization. Participants may have experienced:

* Radiographically documented disease progression during sorafenib therapy or after discontinuation of sorafenib therapy, or

* Discontinuation of sorafenib due to an adverse drug reaction, despite dose reduction by 1 level and BSC

The participant has received sorafenib as the only systemic therapeutic intervention. Any hepatic locoregional therapy that has been administered prior to sorafenib is allowed, but not following sorafenib. Radiation to metastatic sites \[for example (e.g.), bone\] following sorafenib therapy is permitted.

Resolution of clinically significant toxicity of any anti-cancer therapy to Grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events volume 4.0 (NCI-CTCAE v. 4.0).

Adequate Organ Function defined as:

Total bilirubin \<3.0 milligrams/deciliter (mg/dL) \[51.3 micromole/liter (µmol/L)\], aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 × upper limit of normal (ULN)

Serum creatinine ≤1.2 × ULN or calculated creatinine clearance \>50 milliliters/minute (mL/min)

Absolute neutrophil count (ANC) ≥1.0 × 10\^3/microliter (μL) (1.0 × 10\^9/liter (L)\]), hemoglobin ≥9 grams/deciliter (g/dL) \[5.58 millimoles/liter (mmol/L)\], and platelets ≥75 × 10\^3/µL (75 × 10\^9/L)

International Normalized Ratio (INR) ≤1.5 and partial thromboplastin time (PTT) ≤5 seconds above ULN. Participants receiving prophylactic low-dose anticoagulant therapy are eligible provided that INR ≤1.5 and PTT ≤5 seconds above the ULN

The participant's urinary protein is ≤1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates ≥2+ proteinuria, then a 24-hour urine must be collected and must demonstrate \<1000 milligrams (mg) of protein in 24 hours to allow participation in the study

Receiving ongoing therapy with nonsteroidal anti-inflammatory agents (NSAIDs, e.g., indomethacin, ibuprofen, naproxen, nimesulide, celecoxib, etoricoxib, or similar agents) or other antiplatelet agents (e.g., clopidogrel, ticlopidine, prasugrel, dipyridamole, picotamide, indobufen, anagrelide, triflusal). Aspirin (ASA) at doses up to 100 milligrams/day (mg/day) is permitted

Symptomatic congestive heart failure, unstable angina pectoris, or symptomatic or poorly controlled cardiac arrhythmia

Any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization

Uncontrolled arterial hypertension systolic ≥150 / diastolic ≥90 millimeters of mercury (mm Hg) despite standard medical management

Grade 3-4 gastrointestinal bleeding or any variceal bleeding episode in the 3 months prior to randomization requiring transfusion, endoscopic or operative intervention (participants with any bleeding episode considered life-threatening during the 3 months prior to randomization are excluded, regardless of transfusion or intervention status)

Esophageal or gastric varices that require immediate intervention (e.g., banding, sclerotherapy) or represent a high bleeding risk. Participants with evidence of portal hypertension (including splenomegaly) or any prior history of variceal bleeding must have had endoscopic evaluation within the 3 months immediately prior to randomization. Participants with evidence of portal hypertension are eligible for study participation if endoscopic evaluation does not indicate esophageal or gastric varices that require immediate intervention or represent a high bleeding risk; however, these eligible participants must receive supportive therapy (e.g., beta blocker therapy) according to institutional standards and clinical guidelines during study participation

Central nervous system (CNS) metastases or carcinomatous meningitis

History of or current hepatic encephalopathy or current clinically meaningful ascites

What this study is about