advanced biliary tract cancer
Conditions
Interventions
Test group:chemotherapy combined with tirelizumab plus anlotinib
Sponsors
Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18-80 years, ECOGPS score 0-1, with complete behavioral capacity; 2. Patients with advanced gallbladder cancer or cholangiocarcinoma confirmed by histopathology who have not received chemoradiotherapy, immunotherapy or other previous antitumor therapy; 3. According to AJCC 8th edition staging, clinical staging of gallbladder cancer, intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma was cT3/4NXM0/1 or distal cholangiocarcinoma was cT2N2M0 and cT3/4NXM0/1, based on enhanced CT or MRI examination before enrollment; 4. Contraception during the trial; 5. Willingness to provide tumor tissue specimens (fresh tissue specimens or paraffin specimens) obtained from patients after surgery for analysis of PD-L1, MSI, and HER-2 expression; 6. Have at least one measurable lesion according to RECIST 1.1; 7. 7 days before the first study, the organ function level of the enrolled patients must meet the following requirements: (1) Hematopoietic function: absolute neutrophil count (ANC) >= 1.5 x 10^9/L, platelet count (PLT) >= 100 x 10^9/L, hemoglobin (Hb) >= 90 g/L, and no blood transfusion or component blood was received within 14 days before the test; (2) Liver function: serum total bilirubin (TBIL) = 30 g/L, Child-Pugh grade A; (3) Coagulation function: International normalized ratio (INR), activated partial thromboplastin time (APTT) 1 x ULN, FT3 and FT4 levels should be examined at the same time, if FT3 and FT4 levels are normal, you can be enrolled; (5) Renal function: serum creatinine = 50 mL/min, urinary protein 1+, 24-hour urine protein should be measured, and the total amount of urine protein <= 1 gram, you can be enrolled in the study; (6) Normal cardiac function, defined as normal or abnormal ECG examination but not clinically significant, and left ventricular ejection fraction (LVEF) greater than 50% on cardiac ultrasound; 8. Women of childbearing age must have a negative serum pregnancy test result within 7 days before the first administration of the test drug;Fertile men or women with the possibility of pregnancy must use a highly effective contraceptive method (e.g., oral contraceptives, intrauterine devices, controlled sexual desire or barrier contraception combined with spermicide) throughout the trial and continue contraception for 12 months after the end of treatment; 9. Subjects volunteered to join the study, signed the informed consent, had good compliance, and cooperated with follow-up.
Exclusion criteria
Exclusion criteria: 1. Her-2 positive patients; 2. Pregnant or lactating women, and women of childbearing age whose pregnancy test results were positive at baseline; 3. Central nervous system metastases diagnosed by CT and/or MR and/or PET-CT; 4. Previous live vaccination or antitumor therapy such as chemotherapy, radiotherapy or immunotherapy, including gemcitabine, anti-PD-1, anti-PD-L1, anti-PD-L2, and paclitaxel therapy; 5. Patients who have participated in or are participating in clinical trials of other drugs or therapies within 4 weeks before the first administration of the study drug; 6. Patients who underwent major surgery or had not recovered from the side effects of surgery within 4 weeks before the first administration of the study drug, and received radiotherapy within 2 weeks before the first administration of the study drug; 7. The patient has any primary immunodeficiency, active autoimmune disease, or a history of autoimmune disease, including but not limited to:Patients with autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, vitiligo, asthma, asthma remission in childhood, adult without any intervention can be included;Asthma requiring medical intervention with bronchodilators was excluded; 8. Patients with a known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation, and those who were using immunosuppressive agents or steroids for immunosuppressive purposes (dose > 10 mg/day prednisone or other efficacy hormones) and continued to use them within 2 weeks before enrollment; 9. Malignancies other than biliary system malignancies, other than cured basal or squamous cell carcinoma of the skin, superficial bladder cancer, early prostate cancer, cervical cancer in situ or breast cancer, have occurred in the past 5 years; 10. Patients who had received hematopoietic stimulating factors, such as granulocyte colony-stimulating factor (G-CSF) and erythropoietin, within 1 week before the first drug administration; 11. Patients who test positive for antibodies to acquired immunodeficiency virus (HIV) or treponema pallidum, and for active viral hepatitis B or C; 12. Those who are known to be allergic to recombinant humanized PD-1 monoclonal antibody drug and its components; Is known to be allergic to paclitaxels and any excipients thereof;Persons who are known to be allergic to gemcitabine and any of its excipients; 13. Pleural effusion, pericardial effusion, or ascites with symptoms that require clinical treatment; 14. Had severe cardiovascular disease, such as clinically significant coronary heart disease, congestive heart failure with NYHA grade II or higher, uncontrolled arrhythmias, and myocardial infarction, within 12 months before enrollment; 15. The following conditions occurred within 6 months before the first medication: deep vein thrombosis or pulmonary embolism;College myocardial infarction;College serious arrhythmia or instability or angina pectoris; College percutaneous coronary intervention, acute coronary syndrome and coronary artery bypass grafting;Cerebrovascular accident, transient ischemic attack, cerebral embolism. 16. Who has undergone gastrointestinal surgery of any kind, or complicated with upper gastrointestinal obstruction, bleeding, digestive dysfunction, or malabsorption syndrome, which may interfere with the absorption of the study drug; 17. Severe uncontrolled co-infection or other s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR, Objective Remission Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| safety;PFS, Progression-Free Survival;DOR, Duration of Response;6 month Disease Control Rate (DCR);1 year Overall Survival (OS); | — |
Countries
China
Contacts
Public ContactLiu Yingbin
Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
Outcome results
None listed