Regorafenib and Yttrium-90 Transarterial Radioembolization for the Treatment of Unresectable Hepatocellular Cancer

Inclusion Criteria

• Adult patients ages 18 years old and above
• Unresectable HCC
• Child-Pugh A-B7
• Serum bilirubin < 1.5 upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x ULN
• Serum creatinine ≤ 1.5 x ULN
• International normalized ratio (INR)/partial thromboplastin time (PTT) ≤ 1.5 x ULN * NOTE: Participants who are prophylactically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists
• Platelet count > 100,000 platelets/mm^3
• Hemoglobin (Hb) 9 g/dL
• Absolute neutrophil count (ANC) 1,500 neutrophils/mm^3
• Mapping angiogram procedure shows radioembolization is feasible and safe to perform
• No prior systemic therapy for HCC
• Participant agrees to comply with the contraception requirements

Exclusion Criteria

• Angiogram shows vascular shunting which prevents radioembolization
• Prior radioembolization
• Major extrahepatic disease
• Participants with brain metastases
• Participants who have not recovered from major surgery. Participants must not undergo any major surgery at or within 30 days prior to study enrollment
• Presence of a non-healing wound, non-healing ulcer, or bone fracture
• Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy
• Ongoing infection > grade 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0
• Uncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [NCI CTCAE v 5.0] on repeated measurement) despite optimal medical management
• Active or clinically significant cardiac disease including: * Congestive heart failure-New York Heart Association (NYHA) > class II * Active coronary artery disease * Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin * Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before study enrollment, or myocardial infarction within 6 months before study enrollment
• Evidence or history of bleeding diathesis or coagulopathy
• Any hemorrhage or bleeding event ≥ NCI CTCAE grade 3 within 4 weeks prior to start of study medication
• Participants with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of start of study treatment or within 6 months of informed consent
• Participants with any previously untreated or concurrent cancer that is distinct in primary site or histology except cervical cancer in-situ, treated ductal carcinoma in situ of the breast, curatively treated non-melanoma skin carcinoma, noninvasive aerodigestive neoplasms, or superficial bladder tumor. Participants surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before registration are allowed. All cancer treatments must be completed at least 3 years prior to registration
• Participants with impaired decision-making capacity