Primary liver cancer
Conditions
Interventions
Preoperative neoadjuvant immunotherapy group (neoadjuvant sindillizumab treatment group):Sintilimab injection (Sintilimab, Darbersol, is a recombinant fully human monoclonal antibody against programme
The infusion time should be within 30 to 60 minutes. The drug was given once every 3 weeks, twice in total, and surgical treatment was performed within 1 week after the second dose. Continue dosing ev
Direct operation group (non-intervention group, control group):The patient does not receive immunotherapy before surgery, but takes direct surgical treatment. After surgery, it can be decided whether
Sponsors
The First Affiliated Hospital of PLA Army Military Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Inclusion criteria
Inclusion criteria: 1) Age 18-45 years old, gender unlimited; 2) Newly treated patients with hepatocellular carcinoma (MVI not limited) confirmed by histopathology after tumor resection; 3) Resectable patients with stage B BCLC (international standard) with a high risk of recurrence (at least one tumor larger than 5cm in diameter; Or preoperative alpha-fetoprotein greater than 800ug/L; Or the number of tumors greater than 3); 4) Imaging showed that the tumor was intact without rupture; 5) Hepatitis B surface antigen positive, anti-hepatitis B virus treatment is not limited; 6) The tumor did not invade the liver envelope; 7) Accompanied by imaging evidence of cirrhosis or intraoperative cirrhosis; 8) ECOG physical status score 0-1 before operation; 9) Preoperative ASA score =?; 10) The Child-Pugh classification of liver function is class A or B; 11) asymptomatic ascites or ascites requiring therapeutic puncture; 12) Preoperative examination showed no absolute contraindications; 13) have not received systematic treatment before; 14) Based on Response Evaluation Criteria in Solid Tumors (iRECIST), patients with at least one measurable lesion appear as a target lesion. The length of CT/MRI scan =10mm or the short diameter of CT/MRI scan for lymph node lesions =15mm, and the lesions did not receive radiotherapy, freezing or other local treatment; 15) Left ventricular ejection fraction (LVEF) was =55% by echocardiography; 16) Bone marrow function: neutrophils =1.5×109/L, platelets =70×109/L, hemoglobin =90g/L; 17) Liver and kidney function: serum creatinine =1.5 times the upper limit of normal, AST and ALT =2.5 times the upper limit of normal, total bilirubin =1.5 times the upper limit of normal; Urinary protein 2+; If urinary protein =2+, 24-hour quantitative urinary protein must be =1g; 18) The patient had good compliance with the planned treatment, cooperated with the follow-up, understood the research process of the study and signed a written informed consent; 19) To participate in this study voluntarily, the patients themselves choose one of the treatment methods of neoadjuvant immunotherapy or direct surgery; 20) The expected survival period is greater than 6 months; 21) Women of childbearing age should consent to the use of contraceptives (such as intrauterine devices, contraceptives or condoms) during and for six months after the end of medication; For patients who had a negative serum or urine pregnancy test within 7 days prior to inclusion in the study and must be non-lactating, men should consent to use contraceptives during the study period and for 6 months after the study ends; 22) Normal coagulation function, no active bleeding and thrombotic diseases; A. International standardized ratio INR=1.5×ULN; B, partial thromboplastin time APTT=1.5×ULN; C, prothrombin time PT=1.5ULN; 23) Willing to provide tumor lesion excision biopsy tissue;
Exclusion criteria
Exclusion criteria: 1) Prior cytotoxic chemotherapy, biotherapy, radiation therapy, concurrent chemoradiotherapy, or other targeted, immunotherapy (anti-PD-1, anti-PD-L1, anti-PDL-2 or anti-CTLA-4 antibodies or any other antibodies targeting T-cell co-regulatory pathways) for any reason; 2) New York Heart Association (NYHA) score identified as grade II and above heart disease patients; 3) Patients with unstable angina pectoris or myocardial infarction within 6 months; 4) Patients with serious systemic infection or other serious diseases or serious dysfunction of important organs; 5) Have high blood pressure that is not well controlled by antihypertensive medication (systolic blood pressure =140 mm Hg or diastolic blood pressure =90 mm Hg); A history of hypertensive crisis or hypertensive encephalopathy; 6) Patients with known allergy or intolerance to PD-1 monoclonal antibody or its excipients; 7) Active malignant tumors other than liver cancer occurred within the past 5 years or at the same time, except cured skin basal cell carcinoma and cervical carcinoma in situ; 8) Pregnant or lactating women, and patients of childbearing age who refused to take appropriate contraceptive measures during the course of this trial; 9) Participating in other experimental studies within 30 days before the first dose of the investigational drug administration; 10) Patients undergoing two-step hepatectomy (ALPPS) combined with liver segmentation and portal vein ligation; 11) Unwilling to sign informed consent; 12) Other types of benign and malignant liver tumors or mixed liver cancer; 13) is undergoing or has received an organ transplant or allogeneic bone marrow transplant; 14) Patients with moderate to severe ascites needing drainage with clinical symptoms; 15) History of gastrointestinal bleeding, tendency to gastrointestinal bleeding, abdominal fistula, gastrointestinal perforation or abdominal abscess within 6 months before the start of this study; 16) Patients with immune hyperprogression during the period from immunotherapy to surgery; 17) Lower than 60 on the Karnofsky scale; 18) Previous HIV infection; 19) Patients with active, known, or suspected autoimmune diseases. Inclusion is permitted if the patient has vitiligo, type I diabetes, residual hypothyroidism due to an autoimmune disease on hormone replacement therapy, a skin condition that does not require systemic treatment (such as vitiligo, psoriasis, or hair loss), or conditions that are not expected to recur in the absence of external triggers or that the researchers believe will not affect the safety assessment; 20) Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or the evaluation of the study results; 21) Patients with large esophageal varices at risk of bleeding without routine medical intervention; 22) Patients judged by the investigator to be unsuitable for this study;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological tumor response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| objective response rate;Percentage of subjects with reduced tumor size after study drug treatment; event-free survival ;The number of patients who have completed preoperative treatment and continued surgery;Surgical delay rate;Short term surgical results; | — |
Countries
China
Contacts
Public ContactLeida Zhang
The First Affiliated Hospital of PLA Army Military Medical University
Outcome results
None listed