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)
* Previous or current use of sorafenib allowed
* 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 and B 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 \>= 75000 x 10\^6/L
* Hemoglobin (Hgb) \>= 9 g/dL
* Alanine aminotransferase (ALT) =\< 5 x upper limit of normal (ULN)
* Serum creatinine =\< 1.5 x ULN
* 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
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for three months following duration of study participation; should a woman become pregnant, or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
* All subjects must have the ability to understand and the willingness to sign a written informed consent
* Previous or current use of sorafenib and previous use of tamoxifen is allowed as previous systemic therapy

Exclusion Criteria:

* Patients currently receiving any anti-cancer therapy, except sorafenib, 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 history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory)
* Any severe and/or uncontrolled medical conditions including:

  * Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =\< 6 months prior to cycle 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
  * Congenital long QT syndrome
  * Patients with active alcohol intake
  * 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
  * Impairment of gastrointestinal function or who have gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
* 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, family 3, subfamily A (CYP3A) 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
* Pregnant and/or breastfeeding women