Mid to late stage hepatocellular carcinoma
Conditions
Interventions
Test group:After signing informed consent, eligible participants will receive the addition of ipilimumab during first-line targeted immunotherapy. Epilimumab is administered in combination with PD - (
Sponsors
Shanghai GoBroad Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Sign written informed consent before implementing any trial related procedures 2. Age 18-70 years old 3. ECOG PS score is 0-1 4. According to the diagnostic criteria of the Chinese Primary Liver Cancer Diagnosis and Treatment Guidelines (2022 Edition), the initial diagnosis is HCC 5. Barcelona Clinical Liver Cancer (BCLC) staging is stages B and C 6. Child Pugh rating A 7. Expected survival time>3 months 8. According to RECIST 1.1 standard, there should be at least one measurable lesion 9. Total triiodothyronine (T3) or free T3 and free thyroxine (T4) are within the normal range. (Can be controlled through thyroid replacement therapy). Asymptomatic T3, free T3, or free T4 abnormal subjects can be selected 10. Fully control blood pressure 11. It has sufficient organ and bone marrow functions, and the laboratory test values within the first 7 days of random grouping meet the following requirements (no blood components, cell growth factors, albumin, or other corrective treatment drugs are allowed to meet the conditions within the first 14 days of obtaining laboratory tests), as follows: 1) Blood routine: Absolute neutrophil count (ANC) = 1.5 × 109/L; Platelet count (PLT) = 50 × 10 9/L; Hemoglobin content (HGB) = 9.0 g/dL; 2) Liver function: serum total bilirubin (TBIL) = 3 x upper limit of normal value (ULN); Alanine aminotransferase (ALT), aspartate transferase (AST), and alkaline phosphatase (ALP) = 5 × ULN; Serum albumin = 28 g/L; 3) Renal function: serum creatinine (Cr) = 1.5 x ULN or creatinine clearance rate (CCr) = 50mL/min (Cockcroft Gault formula); The urine routine results showed that urine protein<2+; For patients whose baseline urine routine test shows urine protein = 2+, 24-hour urine collection should be conducted and the 24-hour urine protein quantification should be less than 1g; 4) Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) = 1.5 times ULN 12. For female participants of childbearing age, they should undergo a urine or serum pregnancy test with a negative result within 3 days prior to receiving the first study drug administration (day 1 of cycle 1). If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Non reproductive age women are defined as those who have experienced at least one year after menopause, or have undergone surgical sterilization or hysterectomy 13. If there is a risk of conception, all subjects (whether male or female) must use contraceptive measures with an annual failure rate of less than 1% throughout the entire treatment period until 120 days after the last study drug administration (or 180 days after the last chemotherapy drug administration)
Exclusion criteria
Exclusion criteria: 1. Components such as fibroblastic hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and cholangiocarcinoma previously confirmed by histology/cytology 2. History of hepatic encephalopathy or history of liver transplantation 3. Chest fluid, ascites, and pericardial effusion with clinical symptoms that require drainage 4. Acute or chronic active hepatitis B or hepatitis C infected individuals with hepatitis B virus (HBV) DNA>2000IU/ml or 104 copy/ml; Hepatitis C virus (HCV) RNA>103 copies/ml; Hepatitis B surface antigen (HbsAg) and anti HCV antibody are positive at the same time 5. There is central nervous system metastasis 6. There have been incidents of esophageal or gastric variceal bleeding caused by portal hypertension within the past 6 months. Severe (G3) varicose veins were found on endoscopic examination within 3 months prior to the first administration. Evidence of portal hypertension (including imaging findings of splenomegaly), assessed by researchers as high-risk for bleeding 7. Any life-threatening bleeding event that occurred within the past 3 months, including the need for blood transfusion treatment, surgery or local treatment, and continuous medication treatment 8. History of arterial and venous thromboembolism events within the past 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other serious thromboembolism. Implantable venous infusion port or catheter-related thrombosis, or superficial venous thrombosis, except for those with stable thrombosis after routine anticoagulation treatment. Allow prophylactic use of low-dose low molecular weight heparin (such as enoxaparin 40 mg/day) 9. Within 2 weeks before the first administration, use aspirin (>325 mg/day) or other drugs known to inhibit platelet function, such as dipyridamole or clopidogrel, for 10 consecutive days 10. Uncontrollable hypertension, with systolic blood pressure>150mm Hg or diastolic blood pressure>90 mmHg after optimal medical treatment, hypertensive crisis or history of hypertensive encephalopathy 11. Symptomatic congestive heart failure (New York Heart Association classification II-IV). Symptomatic or poorly controlled arrhythmia. History of congenital long QT syndrome or corrected QTc during screening>500ms (calculated using Fridericia method) 12. Severe bleeding tendency or coagulation dysfunction, or undergoing thrombolytic therapy 13. History of gastrointestinal perforation and/or fistula within the past 6 months, history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive intestinal resection (partial or extensive intestinal resection with concurrent chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea 14. Received radiation therapy within 3 weeks prior to the first administration. For patients who received radiation therapy three weeks before the first administration, all of the following conditions must be met before enrollment: currently, there are no radiation related toxic reactions, no corticosteroids need to be taken, and radiation pneumonia, radiation hepatitis, radiation enteritis, etc. are excluded 15. Previous and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severe impairment of lung function, and other lung diseases 16. Active pulmonary tuberculosis (TB)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) of first-line targeted immunotherapy (PD - (L) 1 and anti angiogenic drugs) combined with ipilimumab in patients with advanced hepatocellular carcinoma; | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease progression free time (PFS) assessed by RECIST 1.1 and mRECIST;Total survival time (OS);Disease Control Rate (DCR) assessed by RECIST 1.1 and mRECIST;Continuous response rate (DOR) evaluated by RECIST 1.1 and mRECIST;Security; | — |
Countries
China
Contacts
Public ContactZhou Jun
Shanghai GoBroad Cancer Hospital
Outcome results
None listed