A Multicenter, Randomized, Open-label, Controlled Study of HAIC Combined With Camrelizumab and Apatinib Mesylate for Perioperative Treatment of Resectable Hepatocellular Carcinoma With High-risk Recurrence Factors

A Multicenter, Randomized, Open-label, Controlled Study of HAIC Combined With Camrelizumab and Apatinib Mesylate for Perioperative Treatment of Resectable Hepatocellular Carcinoma With High-risk Recurrence Factors

This study aims to explore the value of the 'HAIC Apatinib Camrelizumab' triple regimen for perioperative treatment of resectable hepatocellular carcinoma. The study adopts a multicenter, randomized, open-label, controlled design and plans to enroll 208 patients, randomly assigned 1:1 to the experimental group and the control group. The experimental group will receive preoperative HAIC combined with targeted-immunotherapy triple regimen neoadjuvant therapy, followed by radical resection, and continue postoperative adjuvant therapy; the control group will undergo surgery directly. The primary endpoint is EFS, and secondary endpoints include R0 resection rate, pCR, MPR, OS, and 1-year/2-year/3-year EFS rates.

Inclusion Criteria:

• 1: 1. Age 18-80, both male and female are acceptable;

  2: 2. Hepatocellular carcinoma (HCC) confirmed by histopathology, cytology, or imaging, with CNLC staging of Ia-IIIa, excluding patients with stage IIIa HCC combined with main portal vein tumor thrombus;

  3: 3. Meets the indications for radical surgical resection;

  4: 4. There are clearly defined high-risk recurrence factors (tumor diameter >5 cm, microvascular invasion, satellite lesions, incomplete tumor capsule, alpha-fetoprotein >400 μg/L, etc.;

  5: 5. ECOG: 0-1;

  6: 6. The functions of major organs have been assessed and meet the requirements for the study treatment;

  7: 7. Has not previously received systematic treatment.

  8: 8. Expected survival time ≥ 12 weeks;

  9: 9. Baseline blood cell count tests and blood biochemistry must meet the following criteria: white blood cell count ≥ 3.0 × 10^9/L; hemoglobin ≥ 90 g/L; absolute neutrophil count ≥ 1.5 × 10^9/L; platelet count ≥ 75 × 10^9/L; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN); total bilirubin ≤ 2 times ULN; serum creatinine ≤ 1.5 times ULN; albumin ≥ 30 g/L;

  10: 10. Women of childbearing age must agree to use contraception (such as intrauterine devices, contraceptive pills, or condoms) during the study period and for 6 months after the end of the study; they must have a negative serum or urine pregnancy test within 7 days prior to enrollment in the study and must not be breastfeeding. Men must agree to use contraception during the study period and for 6 months after the study ends.

  11: 11. The subjects voluntarily joined this study, signed the informed consent form, had good compliance, and cooperated with follow-up.

Exclusion Criteria:

• 1: 1. Merge distant metastases;

  2: 2. Those allergic to camrelizumab and apatinib mesylate;

  3: 3. Previously received systemic or local treatment for liver cancer;

  4: 4. Pleural effusion, pericardial effusion, or ascites accompanied by clinical symptoms and judged by the investigator to require frequent drainage;

  5: 5. History of organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation);

  6: 6. Active or uncontrolled serious infections (≥CTCAE5.0 grade 2 infection), including but not limited to hospitalization due to infectious complications, bacteremia, or severe pneumonia, and unexplained fever >38.5°C before the first dose;

  7: 7. Those with a history of abuse of psychotropic drugs who are unable to quit, or who have mental disorders;

  8: 8.5 Subjects who have had or currently have other malignant tumors requiring active treatment (excluding those that have been adequately treated, such as basal cell or squamous cell skin cancer with an expected 5-year survival rate >90%, carcinoma in situ of the cervix, or carcinoma in situ of the breast);

  9: 9. Presence of uncorrectable coagulation disorders;

  10: 10. Cardiovascular diseases with significant clinical relevance, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass surgery within 6 months prior to enrollment; congestive heart failure New York Heart Association (NYHA) class ≥ 2; ventricular arrhythmias requiring medication (including QTc interval ≥ 450 ms for males, ≥ 470 ms for females); left ventricular ejection fraction (LVEF) <50%;

  11: 11. Severe liver disease (such as cirrhosis), kidney disease, respiratory system diseases, uncontrolled diabetes, or other types of systemic diseases.

  12: 12. Imaging shows that the tumor has invaded major blood vessels, or the researcher judges that during subsequent studies, the tumor is highly likely to invade major blood vessels and cause fatal massive bleeding;

  13: 13. Patients with active autoimmune diseases or immunodeficiency, or with the following medical history, including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, rheumatoid arthritis, inflammatory bowel disease, hypophysitis, vasculitis, nephritis, etc., shall not be included. Exceptions are as follows: patients with a history of autoimmune hypothyroidism who are receiving thyroid hormone replacement therapy may be eligible for the study. Patients with type 1 diabetes whose blood glucose is controlled after insulin therapy may participate in this study.

  14: 14. The patient is using immunosuppressants or systemic hormone therapy to achieve immunosuppression (dose >10mg/day of prednisone or other equivalent steroids, and still using within 2 weeks prior to enrollment);

  15: 15. Experienced arterial/venous thrombotic events within 6 months before the first administration, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral embolism, etc.), deep vein thrombosis, and pulmonary embolism;

  16: 16. The investigator assesses digestive tract diseases or conditions that may affect drug absorption, including but not limited to active gastric and duodenal ulcers, ulcerative colitis, or incompletely resected gastrointestinal tumors with active bleeding, or other conditions deemed by the investigator that may cause gastrointestinal bleeding or perforation, and those with multiple factors affecting oral medication (such as inability to swallow, post-gastrointestinal resection, chronic diarrhea, and intestinal obstruction).

  17: 17. Hypertension not adequately controlled by medication is defined as: systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg;

  18: 18. Underwent surgery (excluding biopsy) within 28 days before being enrolled in this study, or the surgical incision has not completely healed;

  19: 19. Received any other investigational drug treatment or participated in other interventional studies within 4 weeks prior to signing the informed consent form;

  20: 20. Women who are pregnant (positive pregnancy test before medication) or breastfeeding;

  21: 21. According to the researcher's judgment, the patient is considered not suitable for enrollment.