BCLC Stage C Hepatocellular Carcinoma
Conditions
Interventions
Experimental Group:HAIC–palliativeTACE sequential targeted immunotherapy
Sponsors
Affiliated Hospital of Yanbian University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Before implementing any trial-related procedures, sign a written informed consent. 2. Male or female, aged 18 or above; 3. Hepatocellular carcinoma confirmed by imaging or histopathology; 4.BCLC stage C; 5.ECOG score: 0-1 point; 6. Expected survival time >6 months; 7. There is no risk of bleeding after a complete gastroscopy 8. Sufficient organ function. The subjects need to meet the following laboratory indicators: In the absence of granulocyte colony-stimulating factor for the past 14 days, the absolute value of neutrophils (ANC) is greater than or equal to 1.5 × 10^9/L. 2) Without blood transfusion in the past 14 days, the platelet count is greater than or equal to 75×10^9/L. 3) In the past 14 days, without blood transfusion or the use of erythropoietin, the hemoglobin level is greater than 9g/dL. 4) Total bilirubin <=1.5× upper limit of normal value (ULN); 5) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are less than or equal to 3×ULN, serum creatinine is less than or equal to 1.5×ULN, and the creatinine clearance rate (calculated using the Cockcrot-Gault formula 6) is greater than or equal to 50 ml/min. 7) The international normalized ratio (INR) is =2.3 or the prothrombin time (PT) exceeds the normal control range by =6 seconds; 8) Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH exceeds the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled. 9) The myocardial enzyme spectrum is within the normal range (if the researcher comprehensively determines that it is a simple laboratory abnormality without clinical significance, enrollment is also allowed). For female subjects of childbearing age, a urine or serum pregnancy test should be conducted within 3 days prior to the first administration of the study drug (Day 1 of cycle 1), and the result should be negative. If the result of the urine pregnancy test cannot be confirmed as negative, a blood pregnancy test is required. Women of non-childbearing age are defined as those who have been menopausal for at least one year, or have undergone surgical sterilization or hysterectomy. 10. If there is a risk of conception, all subjects (regardless of gender) are required to use contraceptive measures with an annual failure rate of less than 1% throughout the treatment period until 120 days after the last administration of the study drug (or 180 days after the last administration of the chemotherapy drug).
Exclusion criteria
Exclusion criteria: 1. Known cholangiocarcinoma, sarcomatoid hepatocellular carcinoma, mixed hepatocellular–cholangiocarcinoma, or fibrolamellar carcinoma; history of any other active malignancy within the past 5 years or concurrent malignancy other than HCC. Patients with adequately treated, localized malignancies (e.g., basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, superficial bladder cancer, carcinoma in situ of the prostate, cervix, or breast) are eligible. 2. Prior treatment with any of the following therapies:Anti–PD-1, anti–PD-L1, or anti–PD-L2 agents;Agents targeting other stimulatory or co-inhibitory T-cell receptors (e.g., CTLA-4, OX-40, CD137);Targeted therapies inhibiting key oncogenic signaling pathways or regulating tumor growth, proliferation, or angiogenesis, including but not limited to anti-angiogenic agents targeting the VEGF/VEGFR pathway (e.g., lenvatinib), multi-target tyrosine kinase inhibitors (e.g., sorafenib, regorafenib), or precision therapies targeting specific gene alterations (e.g., EGFR, MET, or BRAF inhibitors). 3. Systemic treatment with traditional Chinese medicine with antitumor indications or immunomodulatory agents (including thymosin, interferons, or interleukins) within 2 weeks prior to first dosing. 4. Clinically significant moderate to severe ascites requiring therapeutic paracentesis or drainage, or Child–Pugh score > 7 (patients with minimal ascites detected only by imaging without clinical symptoms are allowed); uncontrolled or moderate-to-large pleural effusion or pericardial effusion. 5. History of hepatic encephalopathy. 6. Active autoimmune disease or history of autoimmune disease with potential for relapse, including but not limited to autoimmune hepatitis, interstitial lung disease, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, or hypothyroidism (patients with hypothyroidism controlled with hormone replacement therapy may be enrolled).Patients with skin disorders not requiring systemic therapy (e.g., vitiligo, psoriasis, alopecia), controlled type I diabetes mellitus on insulin, or childhood asthma completely resolved without adult intervention are eligible. Patients with asthma requiring bronchodilator therapy are excluded. 7. Current interstitial pneumonia or interstitial lung disease (ILD), or a history of ILD requiring steroid treatment; pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), pneumoconiosis, drug-related pneumonitis, idiopathic pneumonia, or evidence of active pneumonia on screening chest CT; severely impaired pulmonary function. Prior radiation pneumonitis confined to the radiation field is allowed. Active tuberculosis is excluded. 8. Known hypersensitivity to bevacizumab, sintilimab, or any excipients of the study drugs. 9. Known history of human immunodeficiency virus (HIV) infection (HIV-1/2 antibody positive). 10.Untreated active hepatitis B infection, defined as HBsAg positivity with detectable HBV-DNA levels above the upper limit of normal at the local laboratory. Note: Patients meeting the following criteria may be enrolled:HBV DNA < 1,000 copies/mL (200 IU/mL) prior to first dosing, with mandatory antiviral therapy throughout chemotherapy to prevent viral reactivation;Patients who are anti-HBc positive, HBsAg negative, anti-HBs negative, and HBV DNA negative do not require prophylactic antiviral therapy but must be closely monitored for viral reactivation. 11. Active hepatitis C infection (HCV antibody posit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate, ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free Survival, PFS;Depth of Response, DpR;Overall Survival,OS;Adverse Events,AEs; | — |
Countries
China
Contacts
Public ContactSongnan Zhang
Affiliated Hospital of Yanbian University
Outcome results
None listed