Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

Inclusion Criteria:

• Ability to take oral drugs
• Diagnosis of advanced hepatocellular carcinoma (HCC) according to the American Association for the Study of Liver Diseases (AASLD) guidelines
• HCC stage B or C according to the Barcelona Clinic Liver Cancer (BCLC)
• No previous systemic therapy for HCC (tamoxifen is allowed as previous systemic therapy)
• Measurable disease according to RECIST, i.e. at least one measurable lesion; this lesion should not have been previously treated with local therapy; a treated lesion may be used where these lesions are the only lesions available for evaluation and have shown definite progression since their last local treatment; local therapy must have been completed at least four weeks prior to baseline evaluation
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Cirrhotic status of current Child-Pugh class A only (5-6 points) with no encephalopathy and no ascites (ascites controlled by diuretics is also excluded in this study); Child-Pugh status should be calculated based on clinical findings and laboratory results during the screening period
• For patients with positive HBV-deoxyribonucleic acid (DNA) and/or positive of hepatitis B surface antigen (HbsAg) results, they must be treated with anti-virals, as prophylaxis at least 1-2 weeks prior to receiving study drug, cycle 1, day 1
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
• Platelets >= 100000 x 10^6/L
• Hemoglobin (Hgb) >= 9 g/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 x upper limit of normal (ULN)
• Serum creatinine =< 1.5 x ULN
• Total bilirubin =< 3.0
• Ability to understand and willingness to sign a written informed consent and to be able to follow the visit schedule
• Life expectancy of approximately 6 months
• For female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control, adequate contraceptives must be used throughout the trial and for 3 months after last study drug administration in both sexes; women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to administration of KD018 and/or sorafenib
• All subjects must have the ability to understand and the willingness to sign a written informed consent
• No previous systemic therapy for HCC is permitted, however, tamoxifen is allowed as previous systemic therapy

Exclusion Criteria:

• Patients currently receiving any anti-cancer therapy or who have received any local anti-cancer therapy =< 4 weeks prior to baseline computed tomography (CT)/magnetic resonance imaging (MRI) scan, prior to cycle 1 treatment
• Active bleeding during the last 30 days prior to cycle 1 treatment including variceal bleeding (esophageal varices should be treated according to standard practice e.g. ligation/banding and procedure completed 30 days prior to cycle 1 treatment
• Patients with a known hypersensitivity to KD018 or known hypersensitivity to sorafenib or contraindications to sorafenib based on the local sorafenib label
• Known previous/current malignancy requiring treatment within =< 3 years except for cervical carcinoma in situ, basal cell carcinoma, and superficial bladder carcinoma
• Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory)
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to course 1 treatment, serious uncontrolled cardiac arrhythmia, uncontrolled hypertension
• Previous transient ischemic attack (TIA), cerebral vascular accident (CVA), symptomatic posterior vitreous detachment (PVD) within last 6 months of cycle 1 treatment
• Patients with active alcohol intake
• Uncontrolled diabetes as defined by glycosylated hemoglobin (HbA1c) > 8%
• Greater or equal grade 3 hypercholesterolemia/hypertriglyceridemia or >= grade 2 hypercholesterolemia/hypertriglyceridemia with history of coronary artery disease (despite lipid-lowering treatment if given)
• Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy, in the opinion of the investigator, except chronic HBV or HCV

• Significant deterioration of lung function, defined as any of the following:

  • 30% decrease in predicted lung volumes, and/or 30% decrease in diffusion capacity of the lung for carbon monoxide (DLCO), and/or =< 88% oxygen (O2) saturation at rest on room air
• Patients receiving chronic treatment with corticosteroids (except for intermittent topical or local injection or aldosterone) or another immunosuppressive agent
• Patients treated with drugs known to be strong inhibitors or inducers of isoenzyme cytochrome P450 3A unless the drugs are medically necessary and no substitutes are available
• Patients who have undergone major surgery =< 2 weeks prior to starting study drug or who have not recovered from surgery
• Patients who have received an investigative drug or therapy within the last 30 days prior to cycle 1 treatment