A Study of BBI608 Administrated With Sorafenib in Adult Patients With Advanced Hepatocellular Carcinoma

Inclusion criteria

• Histologically or diagnosed imaging with hepatocellular carcinoma, and not indicated with a)-d) .

• Radiofrequency ablation therapy (RFA)
• Local therapy [such as percutaneous transhepatic ethanol injection therapy (PEIT), Microwave coagulation therapy (MCT)]
• Transcatheter arterial embolization (TAE)
• Transcatheter arterial chemoembolization (TACE)
• ≥ 20 years of age.
• Not treatment with systemic chemotherapy.
• Signed written informed consent must be obtained and documented.
• Life expectancy ≥ 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Must be Child Pugh Class A.
• Hemoglobin ≥ 8.5 mg/dl.
• Absolute neutrophil count ≥ 1.5 x 10^9 /L.
• Platelets ≥ 75 x 10^9/L.
• Creatinine ≤ 1.5 x ULN.
• Total Bilirubin ≤ 3.0 mg/dl.
• Aspartate Aminotransferase (AST) and Alanine transaminase (ALT) ≤ 5.0 x the upper limit of normal (ULN).
• Females of childbearing potential must have a negative serum pregnancy test.
• Male or female patients of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last BBI608 dose.

Exclusion criteria

• Have had any t a)-i) treatment less than 28 days prior to beginning the enrolment.

• Radiation therapy
• Hormone therapy
• Immune therapy
• Hyperthermia
• Surgical procedure
• Local therapy (such as RFA, PEIT, MCT)
• TAE
• TACE
• other anti- tumour treatment
• Have had a brain metastases with a symptom or requiring treatment.
• Have had coinstantaneous active multiple cancers.
• Have had a carcinomatous pleural effusion, ascites, or cardiac effusion requiring treatment.
• Esophageal varix requiring treatment.
• Patient of pregnancy or possibility of pregnancy, and planning breastfeeding by the end of BBI608 administration after 30days.
• Crohns disease, ulcerative colitis, or historical surgery of extensively small intestine resection.
• Unable or unwilling to swallow BBI608 capsules or Sorafenib tablets.
• Uncontrolled inter-current illness (such as Grade 3active infection, or serious respiratory disease).
• HIV infection.
• Abnormal ECGs which are clinically significant within 28 days before enrolment.
• Patients who are New York Heart Association (NYHA) functional classes III, or IV, or unstable angina.
• Patients newly expressing angina within three months before the enrolment.
• Have had myocardial infarction within six months before the enrolment.
• Administrating with antiarrhythmic drug.
• Have received other investigational products or post-marketing investigational products within 4 weeks of the first dose of BBI608.
• Prior treatment with BBI608.
• Hypersensitivity to Sorafenib or any other component of Sorafenib.
• Ineligible for participation in the study in the opinion of the Investigators.