The purpose of this study is to evaluate the effect of Cabozantinib (XL184) compared with placebo on overall survival in subjects with advanced hepatocellular carcinoma who have received prior sorafenib.

Select Inclusion Criteria:

1. Histological or cytological diagnosis of HCC.
2. The subject has disease that is not amenable to a curative treatment approach.
3. Received prior sorafenib.
4. Progression following at least 1 prior systemic treatment for HCC.
5. Recovery to from toxicities related to any prior treatments.
6. ECOG performance status of 0 or 1.
7. Adequate hematologic and renal function, based upon meeting protocol defined laboratory criteria within 7 days before randomization.
8. Child-Pugh Score of A.
9. Antiviral therapy per local standard of care if active hepatitis B (HBV) infection.
10. 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.
11. Female subjects of childbearing potential must not be pregnant at screening.

Select Exclusion Criteria:

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