Regorafenib and Yttrium-90 Radioembolization for Unresectable Hepatocellular Carcinoma

Eligibility 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.
• 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.