Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib

Select Inclusion Criteria:

• Histological or cytological diagnosis of HCC.
• The subject has disease that is not amenable to a curative treatment approach.
• Received prior sorafenib.
• Progression following at least 1 prior systemic treatment for HCC.
• Recovery to from toxicities related to any prior treatments.
• ECOG performance status of 0 or 1.
• Adequate hematologic and renal function, based upon meeting protocol defined laboratory criteria within 7 days before randomization.
• Child-Pugh Score of A.
• Antiviral therapy per local standard of care if active hepatitis B (HBV) infection.
• Sexually active fertile subjects(male and female)must agree to use medically accepted methods of contraception during the course of the study and for 4 months after the last dose of study treatment.
• Female subjects of childbearing potential must not be pregnant at screening.

Select Exclusion Criteria:

• Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma.
• Receipt of more than 2 prior systemic therapies for advanced HCC.
• Any type of anticancer agent (including investigational) within 2 weeks before randomization.
• Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment within 6 weeks of randomization.
• Prior cabozantinib treatment.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 3 months before randomization.
• Concomitant anticoagulation, at therapeutic doses, with anticoagulants.
• Serious illness other than cancer that would preclude safe participation in the study.
• Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding.
• Moderate or severe ascites.
• Pregnant or lactating females.
• Diagnosis of another malignancy within 2 years before randomization, except for superficial skin cancers, or localized, low-grade tumors.