A Phase 2 Study of Cabozantinib in Japanese Participants With Advanced Hepatocellular Carcinoma

Inclusion Criteria

• Male or female Japanese participants 20 years of age or older on the day of consent.
• Histological or cytological diagnosis of HCC (results of a previous biopsy will be accepted).
• Measurable disease per response evaluation criteria in solid tumors (RECIST) 1.1 as determined by the investigator.
• Participants who have disease that is not amenable to a curative treatment approach (eg, transplant, surgery, radiofrequency ablation).
• Participants who have received 1 or 2 prior anticancer therapies for advanced HCC.
• Cohort A: participants who have received prior sorafenib.
• Cohort B: participants who have not received prior sorafenib. Note: Additional prior systemic therapies used as adjuvant or local therapy are allowed.
• Radiographic progression following prior systemic anticancer therapy for advanced HCC.
• Recovery to = =1,200/mm^3.
• Platelets >=60,000/mm^3.
• Hemoglobin >=8 g/dL.
• Serum creatinine = =40 mL/min using the Cockroft-Gault equation.
• Urine protein-to-creatinine ratio (UPCR) = =2.8 g/dL.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 150 mm Hg systolic, or >100 mm Hg diastolic despite optimal antihypertensive treatment.
• Stroke (including transient ischemic attack [TIA]), myocardial infarction, or other ischemic event within 6 months before Week 1 Day 1.
• Thromboembolic event within 3 months before Week 1 Day 1.
• A left-ventricular ejection fraction = 0.5 teaspoon (>2.5 mL) of red blood, or other signs indicative of pulmonary hemorrhage, or history of other significant bleeding if not due to reversible external factors.
• Other clinically significant disorders such as:
• Active infection requiring systemic treatment.
• Known infection with human immunodeficiency virus, or known acquired immunodeficiency syndrome -related illness.
• Active hepatitis B and/or C. Participants with active hepatitis virus infection controlled with antiviral therapy are eligible.
• Serious non-healing wound/ulcer/bone fracture.
• Malabsorption syndrome.
• Uncompensated/symptomatic hypothyroidism.
• Requirement for hemodialysis or peritoneal dialysis.
• History of solid organ transplantation.
• Participants with untreated or incompletely treated varices with bleeding or high risk for bleeding. Participants treated with adequate endoscopic therapy (according to institutional standards) without any episodes of recurrent GI bleeding requiring transfusion or hospitalization for at least 6 months before Week 1 Day 1 are eligible.
• Moderate or severe ascites.
• Corrected QT interval calculated by the Fridericia formula (QTcF) >500 msec within 14 days before Week 1 Day 1.

Note: If the QTcF is >500 msec in first electrocardiogram (ECG), a total of 3 ECGs each separated by at least 3 minutes should be performed within 30 minutes. If the average of these 3 consecutive results for QTcF is =<500 msec, the participant meets eligibility in this regard.

• Inability to swallow tablets.
• Previously identified allergy or hypersensitivity to components of the study treatment formulations.
• Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.

Note: Female participants who are in the lactation period, even if they discontinue breastfeeding, will be excluded from the study.

• Previously diagnosed with another malignancy and have any evidence of residual disease within 2 years before Week 1 Day 1.

Note: Participants with superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy are not excluded.

• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of Cabozantinib.
• Use of strong cytochrome P450 (CYP) 3A inhibitors and CYP3A inducers