Shuganhuazhuo Formula for Advanced Hepatocellular Carcinoma With Damp-Heat Syndrome

• Shuganhuazhuo Formula (Drug): The Shuganhuazhuo Formula is composed of the following medicinal materials: Bupleuri Radix (Chaihu), Scutellariae Radix (Huangqin), processed Pinelliae Rhizoma (Fabanxia), Ginseng Radix et Rhizoma (Renshen, sliced), Agrimoniae Herba (Xianhecao), stir-fried Arecae Semen (Chao Binglang), stir-fried Aurantii Fructus (Chao Zhiqiao), Artemisiae Scopariae Herba (Yinchen), and other ingredients.The formula contains no toxic or strongly drastic medicinal substances, and the dosages of all herbal ingredients are within the ranges specified in the Pharmacopoeia of the People's Republic of China (2025, Volume I).
• Targeted therapy (Drug): Targeted therapy, with agents including but not limited to regorafenib and apatinib.
• Immunotherapy (Drug): Immunotherapy, with agents including but not limited to ramucirumab, pembrolizumab, camrelizumab, and tislelizumab.
• Chemotherapy (Drug): Chemotherapy, including but not limited to the FOLFOX4 regimen.
• TACE (Procedure), also known as Transcatheter Arterial Chemoembolization: Transcatheter Arterial Chemoembolization(TACE)
• HAIC (Procedure), also known as Hepatic Arterial Infusion Chemotherapy: Hepatic Arterial Infusion Chemotherapy(HAIC), including but not limited to the FOLFOX regimen.

Primary outcomes

• Liver reserve function [Through baseline and intervention period, up to 6 months.]: Assessment is based on the indocyanine green retention rate at 15 minutes (ICG-R15) from the indocyanine green clearance Test.

Secondary outcomes

• Overall Survival [Through study completion, an average of 2 years.]: The time elapsed from the subject's randomization to death due to any cause.
• Health-related Quality of Life [Through baseline and intervention period, up to 6 months.]: Assessment is conducted using the European Organization for Research and Treatment of Cancer's Core Quality of Life Scale (EORTC QLQ-C30) combined with the 18 items of the Hepatocellular Liver Carcinoma-Specific Quality of Life Supplement Module (EORTC QLQ-HCC18).

Other outcomes

• Incidence of adverse reactions [Through study completion, an average of 1 year.]: During the study, the incidence of adverse events (AEs) that are assessed as Definite, Probable, or Possible to the trial drug is determined. The assessment of the relationship between adverse events and the trial drug is conducted in accordance with the "Technical Guidelines for Evaluating the Association between Adverse Events and Drugs in Clinical Trials" issued by the National Medical Products Administration's Center for Drug Evaluation. The five-point attribution scale developed by the Cancer Treatment Evaluation Program (CTEP) of the National Cancer Institute in the United States is also used for evaluation.
• Incidence of severe adverse reactions [Through study completion, an average of 1 year.]: During the study, the incidence of adverse events (AEs) that are assessed as Definite, Probable, or Possible to the trial drug is determined. The assessment of the relationship between adverse events and the trial drug is conducted in accordance with the "Technical Guidelines for Evaluating the Association between Adverse Events and Drugs in Clinical Trials" issued by the National Medical Products Administration's Center for Drug Evaluation. The five-point attribution scale developed by the Cancer Treatment Evaluation Program (CTEP) of the National Cancer Institute in the United States is also used for evaluation.

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

1. According to the National Health Commission(China)'s "Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2026)", clinically or pathologically diagnosed as primary liver cancer.
2. Barcelona Clinic Liver Cancer (BCLC) stage is C.
3. Planning to receive second-line or third-line anti-tumor therapies.
4. The dominant syndrome in traditional Chinese medicine diagnosis is damp or heat.
5. Age: ≥ 18 years and ≤ 75 years.

Exclusion Criteria:

1. Expected survival is less than 3 months.
2. Definitive pathological diagnosis of intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma (cHCC-CCA).
3. Comorbid severe heart, liver, kidney dysfunction:

   1. heart

      * New York Heart Association(NYHA) cardiac function > class II
   2. liver

      * aspartate aminotransferase > 3 times the upper limit of normal
      * alanine aminotransferase > 3 times the upper limit of normal
      * bilirubin > 3 times the upper limit of normal
   3. kidney

      * creatinine clearance (Cockcroft-Gault) < 60 mL/min)
4. Concurrent with other malignant tumors.

• Li Bing, PhD., Study chair, HerbMed Group Co., Ltd.