Observing the Efficacy and Safety of Icaritin Soft Capsules as Postoperative Adjuvant Therapy in Hepatocellular Carcinoma Patients with High-Risk Factors for Recurrence (A Single-Arm, Single-Center, Prospective Clinical Study Protocol)

Detailed Description:

Primary Endpoint:

Recurrence-Free Survival (RFS)

Secondary Endpoints:

Recurrence-Free Survival Rate (RFSR) at 6 months and 12 months, Overall Survival (OS) , Quality of Life (QoL) , Safety (including incidence and severity of Adverse Events [AEs] and Serious Adverse Events [SAEs]).

Inclusion Criteria:

• Age ≥ 18 years.
• Clinically or histologically/cytologically confirmed hepatocellular carcinoma (HCC) per the Primary Liver Cancer Diagnosis and Treatment Guidelines (2022 Edition). Archived tissue samples are permitted; if no prior histological diagnosis exists, fresh tumor biopsy must be performed at baseline.
• At least one measurable lesion (RECIST v1.1).
• Child-Pugh score ≤ 7.
• Patients who underwent R0 resection (postoperative pathology report required) and showed no residual intrahepatic lesions on MRI within 8 weeks after surgery.
• At least one high-risk recurrence factor:
• Tumor size ≥ 5 cm;
• Tumor number ≥ 3;
• Microvascular invasion (MVI) grade: M1 or M2;
• Portal vein tumor thrombus resection (Cheng's classification I or II).
• No prior systemic therapy for HCC.
• Normal major organ function, with laboratory results meeting the following
• criteria within 7 days before treatment:
• Hemoglobin > 80 g/L;
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
• Platelet count ≥ 40 × 10⁹/L;
• Serum albumin ≥ 28 g/L;
• Total bilirubin ≤ 2 × upper limit of normal (ULN);
• AST/ALT ≤ 5 × ULN;
• Alkaline phosphatase (ALP) ≤ 2.5 × ULN;
• Serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min.
• Coagulation function: International normalized ratio (INR) ≤ 1.5 × ULN or prothrombin time (PT) ≤ 16 s.
• Ability to swallow and absorb oral medication.
• Negative serum pregnancy test within 7 days before randomization for women of childbearing potential; agreement to use effective contraception during treatment and for 60 days after the last dose.
• Voluntary participation with signed informed consent and expected good compliance.

Exclusion Criteria:

• Prior systemic therapy for HCC, including chemotherapy, targeted agents (e.g., sorafenib, lenvatinib, regorafenib), immune modulators (anti-PD-1/PD-L1/CTLA-4), or modern Chinese medicine with antitumor indications. Concurrent use of any investigational drug (except antiviral therapy) is excluded.
• Recurrent or metastatic HCC.
• Clinically significant ascites, pleural effusion, or pericardial effusion uncontrolled by medication at enrollment.

(Note: Imaging-detected ascites without clinical symptoms is permitted.)

• History of abdominal wall fistula, gastrointestinal perforation, refractory unhealed gastric ulcer, or active gastrointestinal bleeding within 6 months before enrollment.
• HCC lesion(s) ≥ 10 cm in any dimension (confirmed by BICR), > 10 lesions, or HCC volume ≥ 50% of liver volume; macrovascular portal vein tumor thrombosis.
• Major cardiovascular impairment within 12 months before treatment:
• NYHA Class II+ heart failure;
• Unstable angina, myocardial infarction, or stroke;
• Arrhythmia with hemodynamic instability;
• QTc interval > 480 ms.
• Any surgery within 28 days before the first dose.
• History or current diagnosis of coagulopathy, bleeding, or thrombotic disorders.
• Clinically significant liver disease, including active viral hepatitis, alcoholic hepatitis, decompensated cirrhosis, severe fatty liver, hereditary liver disease, liver atrophy, superior vena cava syndrome, or portal hypertension.

(Note: Portal hypertension without ascites, jaundice, or gastrointestinal bleeding may be considered.)

• Active autoimmune disease requiring systemic therapy within the past 2 years.
• Live vaccine administered within 30 days before the first dose.
• Hypersensitivity to any component of Epimedium Soft Capsules.
• Uncontrolled active HBV, HCV, or HDV infection; active tuberculosis.
• Pregnancy, lactation, or unwillingness to use contraception during the study.
• Any condition that may contraindicate the study drug, compromise data reliability, increase treatment risk, or affect compliance (e.g., metabolic disorders, abnormal lab results).
• Investigator judgement of unsuitability for the study.