Drug Combination Therapy (Sorafenib, Sonidegib, and Irinotecan) for the Treatment of Patients with Advanced Hepatocellular Carcinoma, AD HOC Trial

Inclusion Criteria

• Adults >= eighteen years of age
• Biopsy-proven advanced-stage hepatocellular carcinoma (HCC), as confirmed by pathological analysis, or confirmation of HCC from a Liver Imaging Reporting & Data System (LI-RADS) 5 imaging score
• Not eligible for, or had disease progression after, surgical or locoregional therapies when these treatments are intended as sole, definitive therapy aimed at curing the disease, rather than as part of a combination therapy approach
• Subjects must not have more than one active malignancy at the time of enrollment (subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen [as determined by the treating physician and approved by the principle investigator (PI)] may be included)
• Eastern cooperative oncology group (ECOG) performance status score of 2 or less
• Child–Pugh liver function class A or B7
• Life expectancy of 12 weeks or more
• At least one target lesion that could be measured in one dimension, according to the Response Evaluation Criteria in Solid Tumors (modified [m]RECIST)
• Platelet count >= 60,000
• Hemoglobin, >= 8.0 g/dL
• International normalized ratio (INR) =< 2.5
• Albumin >= 2.5 g/dL
• Total bilirubin, =< 5 mg/dL
• Alanine aminotransferase (ALT) & aspartate aminotransferase (AST) =< 5 times the upper limit of the normal range
• Creatinine =< 2 times the upper limit of the normal range
• Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures
• Subjects of childbearing potential (SOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 20 months after the last dose of study drug to minimize the risk of pregnancy. Prior to study enrollment, subjects of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. SOCBP includes any subject who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as: * Amenorrhea that has lasted for >= 12 consecutive months without another cause, or * For subjects with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL
• Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 8 months following the last dose of study drug

Exclusion Criteria

• Subjects of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 20 months after the last dose of study drug
• Subjects who are pregnant or breastfeeding
• History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications or protocol noncompliance, in the opinion of the treating physician
• Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness
• Inability to follow up with treatment center for up to 12 weeks after enrollment
• Anticipated major surgery during the time of planned study
• Homozygosity for UGT1A1*28 via genotyping