Phase 1b/2 Study of Oprozomib in Combination With Sorafenib in Subjects With Advanced Hepatocellular Carcinoma

Exclusion Criteria

• •1. Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical and breast carcinoma in situ, adequately treated basal cell or squamous cell carcinoma of the skin, or superficial bladder tumors (Ta, Tis \& T1)
• •2. Renal failure requiring hemo- or peritoneal dialysis
• •3. History of cardiac disease
• •4. Active clinically serious infections. Hepatitis B is allowed if no active replication is present. Hepatitis C is allowed if no antiviral treatment is required
• •5. Known history of human immunodeficiency virus (HIV) infection
• •6. Known history or symptomatic metastatic brain or meningeal tumors
• •7. Clinically significant gastrointestinal (GI) bleeding, serious nonhealing wound and ulcer within 3 months prior to study entry, or bone fracture within 30 days prior to study entry
• •8. History of organ allograft
• •9. Known or suspected allergy to the investigational agent or any agent given in association with this trial
• •10. Inability to swallow medication, inability or unwillingness to comply with the drug administration requirements, or GI condition that could interfere with the oral absorption or tolerance of treatment
• •11. Uncontrolled diabetes
• •12. Any contraindication to oral hydration (e.g., preexisting cardiac impairment or fluid restriction)
• •13. Uncontrolled ascites
• •14. Pleural effusion or ascites that causes respiratory compromise (NCI-CTCAE ≥ Grade 2 dyspnea).
• •15. Women who are pregnant and/or breastfeeding
• •16. Prior use of any systemic anticancer chemotherapy for HCC
• •17. Prior use of systemic investigational agents for HCC
• •18. Concomitant treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors
• •19. Known hypersensitivity or intolerance to dexamethasone or 5-HT3 antagonist