Regorafenib and Yttrium-90 Radioembolization for Unresectable Hepatocellular Carcinoma

Inclusion Criteria: 1. Adult patients ages 18 years old and above. 2. Unresectable Hepatocellular Carcinoma (HCC). 3. Child-Pugh A-B7. 4. Serum bilirubin \< 1.5 upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 5 x ULN. 5. Serum creatinine ≤ 1.5 x ULN. 6. 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. 7. Platelet count \> 100,000 platelets/mm3, hemoglobin (Hb) 9 g/dL, and absolute neutrophil count (ANC) 1,500 neutrophils/mm3. 8. Mapping angiogram procedure shows radioembolization is feasible and safe to perform. 9. No prior systemic therapy for HCC. 10. Participant agrees to comply with the contraception requirements as described in protocol. Exclusion Criteria: 1. Angiogram shows vascular shunting which prevents radioembolization. 2. Prior radioembolization. 3. Major extrahepatic disease. 4. Participants with brain metastases. 5. Participants who have not recovered from major surgery. Participants must not undergo any major surgery at or within 30 days prior to study enrollment. 6. Presence of a non-healing wound, non-healing ulcer, or bone fracture. 7. Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy. 8. Ongoing infection \> Grade 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0. 9. Uncontrolled hypertension (systolic pressure \> 140 mm Hg or diastolic pressure \> 90 mm Hg \[NCI CTCAE v5.0\] on repeated measurement) despite optimal medical management. 10. Active or clinically significant cardiac disease including: 1. Congestive heart failure - New York Heart Association (NYHA) \> Class II. 2. Active coronary artery disease. 3. Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin. 4. Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before study enrollment, or myocardial infarction within 6 months before study enrollment. 11. Evidence or history of bleeding diathesis or coagulopathy. 12. Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of study medication. 13. 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. 14. 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 nonmelanoma 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. 15. Participants with impaired decision-making capacity.