Potentially resectable intrahepatic cholangiocarcinoma with a high risk of recurrence
Conditions
Interventions
Experimental Group:GEMOX regimen combined with tislelizumab and donafenib
Sponsors
Hunan Provincial People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1) Voluntary enrollment and signed written informed consent; 2) Age of 18-75 years old (inclusive), male or female; 3) intrahepatic cholangiocarcinoma confirmed by histopathology; 4) Preoperative assessment of ICC staging as T1-4,N0-1,M0; 5) Imaging evaluation was initially technically resectable, that is, the lesion was limited to one half of the liver and the remaining functional liver volume ratio (FLR/SLV) >= 40%, ICG 15R5cm; 1.Local area Regional lymph nodes were positive. The presence of satellite or multifocal lesions, or radiological suspicion of tumor adhesion to the diaphragm; 2.CA199 > 200U/ml; 3.The estimated surgical margin width was less than 1cm; 7) have not received any previous anti-tumor therapy, including surgery, chemoradiotherapy, targeted therapy, and immunotherapy; 8) no obstructive jaundice and obstruction of large vessels (main portal vein and inferior vena cava); 9) Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0-1; 10) Child-pugh A liver function; 11) expected survival time > 3 months; 12) Female patients of childbearing potential (i.e., not menopausal or not surgically sterilized) must have a negative serum pregnancy test within 7 days prior to administration of the study drug; 13) Female or male patients of childbearing potential must use reliable contraception during the use of the study drug and for 60 days after the last dose; 14) Major organ function must be normal, meaning compliance with the following criteria:Complete blood count (no transfusion or use of G-CSF within 14 days prior to screening):a) Hemoglobin >= 90 g/L;b) Absolute neutrophil count (ANC) >= 1.5×10^9/L;c) Platelet count >= 75×10^9/L;
Exclusion criteria
Exclusion criteria: 1) mixed tumor components with histologically/cytologically confirmed hepatocellular carcinoma and ampullary carcinoma; 2) A history of malignancy, unless the following criteria are met: Patients have received potentially curative treatment and have had no evidence of the disease for 5 years; 1.The patients successfully received resection of skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, and cervical cancer Carcinoma in situ and other carcinoma in situ; 3) recurrence or distant metastasis was diagnosed before enrollment. Distant metastasis criteria: imaging and intraoperative biopsy suggested peritoneum Implant, lung, brain, bone, or other organ metastasis. 4) bile duct obstruction with incomplete recovery; 5) a history of severe mental illness; 6) have a disease that affects absorption, distribution, metabolism, or clearance of the study drug (e.g., severe vomiting, chronic diarrhea, Intestinal obstruction, malabsorption, etc.); 7) received potent CYP3A4 inhibitors within 7 days before randomization or within 12 days before study enrollment Those treated with potent CYP3A4 inducers; 8) aspirin (> 325 mg/ day) or other known therapies for 10 consecutive days within 2 weeks before the first dose Drugs that inhibit platelet function such as dipyridamole or clopidogrel; 9) Patients with a known or suspected allergy to donafenib, or allergies to the excipients of the investigational drug; 10) Those with active bleeding or coagulation disorders, bleeding tendencies, or currently receiving thrombolytic, anticoagulant, or antiplatelet therapy; 11) History of gastrointestinal bleeding within the past 4 weeks or a clear tendency for gastrointestinal bleeding (e.g., known local active ulcer lesions, positive fecal occult blood; if fecal occult blood persists, a gastroscopy should be performed), or other conditions that the investigator considers may cause gastrointestinal bleeding (e.g., severe gastric/esophageal varices); 12) History of esophageal or gastric variceal bleeding due to portal hypertension within the past 6 months. Severe (G3) varices known by endoscopy within 3 months prior to initial dosing. Evidence of portal hypertension (including splenomegaly detected on imaging) with high bleeding risk as assessed by the investigator; 13) History of gastrointestinal perforation, abdominal fistula, or intra-abdominal abscess within the past 6 months; 14) History of thrombosis or thromboembolic events within the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc.; 15) Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction within the past 6 months, severe/unstable angina or coronary artery bypass grafting, congestive heart failure (New York Heart Association NYHA class > 2), poorly controlled arrhythmias requiring pacemaker therapy, or uncontrolled hypertension (systolic >= 140 mmHg and/or diastolic >= 90 mmHg); 16) Active infections, including:a) HIV (HIV1/2 antibody) positive;b) Active tuberculosis;c) Other uncontrolled active infections (CTCAE V5.0 > grade 2); 17) Moderate to severe ascites or pleural effusion; 18) Other significant clinical or laboratory abnormalities that the investigator believes may affect safety evaluation, such as uncontrolled diabetes, chronic kidney disease, peripheral neuropathy grade II or higher (CTCAE V5.0), thyroid dysfunction, etc.; 19) Pregnant or breastfeeding women,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| event-free survival (EFS),; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR);disease control rate (DCR);R0 resection rate;disease-free survival (DFS);major pathological response rate (MPR);Overall survival (OS);Analysis of adverse events and serious adverse events; | — |
Countries
China
Contacts
Public ContactPeng Chuang
Hunan Provincial People's Hospital
Outcome results
None listed