Shuganhuazhuo Formula for Advanced Hepatocellular Carcinoma With Damp-Heat Syndrome

Official title

Shuganhuazhuo Formula (Chinese Herbal Medicine) in the Combined Treatment of Advanced Hepatocellular Carcinoma With Damp-Heat and Blood Stasis Syndrome: An Open-Label Randomized Controlled Trial

Overview

Primary liver cancer is a malignant tumor with a very poor prognosis. Hepatocellular carcinoma(HCC) accounts for approximately 80% of cases. Under the current targeted and immunotherapy-based treatment approaches, the overall survival of patients with advanced HCC has improved significantly compared to targeted therapy alone. However, there are still limitations in therapeutic effectiveness. In addition to the tumor burden, liver reserve function is associated with the prognosis of HCC. Cirrhosis, tumor burden, and anti-tumor treatment can all lead to damage to liver reserve function, which in turn leads to a decrease in patient survival. Currently, there are no specific treatments for deteriorating liver reserve function; only symptomatic treatments such as reducing transaminase levels, bilirubin levels, and blood ammonia levels, as well as diuretics, are available. The indocyanine green(ICG) clearance test allows for precise, dynamic, and quantitative measurement of liver clearance function, making it a commonly used method for assessing liver reserve function in clinical practice.Previous studies have confirmed that its test results are closely related to the prognosis of HCC. Shuganhuazhuo Formula(SHF) is a Chinese herbal medicine used to treat advanced HCC with syndrome of Damp-Heat and Blood stasis. It can inhibit necrosis in the livers of mice in experimental models, reduce fibrosis scores, and demonstrate potential therapeutic effects in protecting the liver, reducing oxidative stress, and preventing fibrosis. This study is an open-label randomized controlled trial. Patients with advanced HCC who are receiving second-line or third-line anti-tumor treatment are randomly assigned in a 1:1 ratio to either the control group or the traditional Chinese medicine (TCM) group. The control group receives anti-tumor treatment as recommended by guidelines, while the TCM group receives additional treatment with SHF. SHF involves decocting traditional Chinese medicine ingredients twice daily. Each time, 150 ml of the decoction is prepared and taken orally half an hour after breakfast and dinner. Treatment lasts for 6 months. During this period, the ICG clearance test is performed every 2 months to assess liver reserve function, and quality of life is also evaluated. After the treatment period, follow-ups on survival and safety are conducted every 3 months. This study aims to evaluate the benefits of the SHF in terms of liver reserve function, overall survival, and quality of life in patients with HCC of the syndrome of Damp-Heat and Blood stasis. It also includes exploratory analyses of differences in biomarker expression during treatment.

Interventions

• Drug Shuganhuazhuo Formula
  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 ingredi
• Drug Targeted therapy
  Targeted therapy, with agents including but not limited to regorafenib and apatinib.
• Drug Immunotherapy
  Immunotherapy, with agents including but not limited to ramucirumab, pembrolizumab, camrelizumab, and tislelizumab.
• Drug Chemotherapy
  Chemotherapy, including but not limited to the FOLFOX4 regimen.
• Procedure TACE
  Transcatheter Arterial Chemoembolization(TACE)
• Procedure HAIC
  Hepatic Arterial Infusion Chemotherapy(HAIC), including but not limited to the FOLFOX regimen.

Primary outcome measures

• Liver reserve function [Time frame: Through baseline and intervention period, up to 6 months.]

Secondary outcome measures (2)

• Overall Survival [Time frame: Through study completion, an average of 2 years.]
• Health-related Quality of Life [Time frame: Through baseline and intervention period, up to 6 months.]

Eligibility criteria

Inclusion criteria

• 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.
• Barcelona Clinic Liver Cancer (BCLC) stage is C.
• Planning to receive second-line or third-line anti-tumor therapies.
• The dominant syndrome in traditional Chinese medicine diagnosis is damp or heat.
• Age: ≥ 18 years and ≤ 75 years.

Exclusion criteria

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

• heart

• New York Heart Association(NYHA) cardiac function > class II
• 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
• kidney

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Zhejiang Cancer Hospital — Hangzhou

Identifiers

NCT: NCT07691645 · IIT-2026-288

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗