Hepatocellular carcinoma
Conditions
Interventions
treatment group:sintilimab+bevacizumab
Sponsors
The Third Affiliated Hospital of Naval Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent must be obtained before any trial-related procedures are implemented. 2. Age between 18-70 years old. 3. ECOG PS score of 0-1. 4. Diagnosed with hepatocellular carcinoma according to the Chinese Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2022 edition). 5. Barcelona Clinic Liver Cancer (BCLC) stage B or C. 6. Previously received first-line treatment with immunotherapy combined with TKIs, where immunotherapies include but are not limited to Pembrolizumab, Durvalumab, Nivolumab, Atezolizumab, Sintilimab, Tislelizumab, Camrelizumab; and TKIs include but are not limited to Sorafenib, Lenvatinib, Donafenib, Apatinib, Anlotinib. 7. Child-Pugh score = 7. 8. Expected survival time > 3 months. 9. At least one measurable lesion according to RECIST1.1 criteria. 10. Total triiodothyronine (T3) or free T3 and free thyroxine (T4) within the normal range (can be controlled by thyroid replacement therapy). Asymptomatic subjects with abnormal T3, free T3, or free T4 can be enrolled. 11. Blood pressure is well controlled. 12. Adequate organ and bone marrow function, with laboratory values within the following ranges within 7 days before randomization (meeting the criteria without any corrective treatment such as blood components, growth factors, albumin, or other medications within 14 days before obtaining the laboratory values), specifically: 1). Hematology: Absolute neutrophil count (ANC) = 1.5×10^9/L; Platelet count (PLT) = 75×10^9/L; Hemoglobin (HGB) = 9.0 g/dL; 2). Liver function: Serum total bilirubin (TBIL) = 3× upper limit of normal (ULN); Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) = 5× ULN; Serum albumin = 28 g/L; 3). Renal function: Serum creatinine (Cr) = 1.5× ULN or creatinine clearance (CCr) = 50 mL/min (Cockcroft-Gault formula); Urinalysis shows proteinuria < 2+; For patients with baseline proteinuria = 2+, a 24-hour urine protein collection should be performed, and the 24-hour urine protein should be < 1g; 4). Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) = 1.5× ULN. 13. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 3 days before receiving the first dose of study medication (Day 1 of Cycle 1). If the urine pregnancy test result is indeterminate, a blood pregnancy test is required. Women not of childbearing potential are defined as those who have been postmenopausal for at least one year, or have undergone surgical sterilization or hysterectomy. 14. All subjects (both male and female) with reproductive potential must use contraceptive measures with a failure rate of less than 1% per year throughout the study period and for 120 days after the last dose of study medication (or 180 days after the last dose of chemotherapy).
Exclusion criteria
Exclusion criteria: 1. Previously histologically/cytologically confirmed hepatocellular carcinoma with fibrolamellar, sarcomatoid, or cholangiocarcinoma components. 2. Previous treatment with large molecule anti-angiogenic drugs such as Bevacizumab. 3. History of hepatic encephalopathy or liver transplantation. 4. Diagnosed with decompensated liver cirrhosis. 5. Clinically symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage. 6. Central nervous system metastasis. 7. Esophageal or gastric variceal bleeding due to portal hypertension within the past 6 months. Severe (G3) varices found in endoscopy within 3 months prior to the first dose. High risk of bleeding assessed by the investigator based on evidence of portal hypertension (including splenomegaly on imaging). 8. Any life-threatening bleeding event within the past 3 months, including those requiring transfusion, surgery, local treatment, or continuous medication. 9. Arterial or venous thromboembolic events within the past 6 months, including myocardial infarction, unstable angina, stroke, transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other serious thromboembolic event. Thrombi formed due to implantable venous access devices or catheter-related thrombosis, or superficial vein thrombosis, stabilized after conventional anticoagulant therapy, are exceptions. Prophylactic use of low-dose low molecular weight heparin (e.g., enoxaparin 40 mg/day) is allowed. 10. Continuous use of aspirin (> 325 mg/day) or other drugs known to inhibit platelet function such as dipyridamole or clopidogrel within 2 weeks prior to the first dose. 11. Uncontrolled hypertension, systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg despite optimal medical treatment, or history of hypertensive crisis or hypertensive encephalopathy. 12. Symptomatic congestive heart failure (New York Heart Association Class II-IV). Symptomatic or poorly controlled arrhythmia. History of congenital long QT syndrome or corrected QTc > 500 ms (using Fridericia’s formula) at screening. 13. Severe bleeding tendency or coagulation disorder, or receiving thrombolytic therapy. 14. History of gastrointestinal perforation and/or fistula within the past 6 months, history of bowel obstruction (including incomplete bowel obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small intestine resection with chronic diarrhea), Crohn’s disease, ulcerative colitis, or chronic diarrhea. 15. Radiation therapy within 3 weeks prior to the first dose. For patients who received radiation therapy more than 3 weeks prior to the first dose, they must meet all of the following criteria to be enrolled: no radiation-related toxicity currently, no need for corticosteroids, exclusion of radiation pneumonitis, radiation hepatitis, or radiation enteritis. 16. History or presence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, or severely impaired lung function. 17. Active pulmonary tuberculosis (TB) or receiving anti-tuberculosis treatment or having received anti-tuberculosis treatment within 1 year prior to the first dose. 18. HIV infection (HIV 1/2 antibody positive) or known syphilis infection. 19. Any active autoimmune disease or history of autoimmune disease (including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism). 20
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease control rate;progression-free survival;Duration of response;overall survival;safety; | — |
Countries
China
Contacts
Public ContactXuying Wan
The Third Affiliated Hospital of Naval Medical University
Outcome results
None listed