biliary tract cancer
Conditions
Interventions
Neoadjvant Group:Neoadjuvant therapy: GS+PD-1 regimen, 3 weeks/cycle, 2 cycles
Combined adjuvant therapy: S1+PD-1 regimen, 3 weeks/cycle, 8 cycles
Sponsors
Shanghai Eastern Hepatobiliary Surgery Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent prior to the implementation of any trial-related procedures 2. Male or female= 18 years old, = 75 years old 3. Histologically or cytologically confirmed tumors of the biliary system (including intrahepatic cholangiocarcinoma, gallbladder cancer and extrahepatic cholangiocarcinoma), and the lesions are resectable as assessed by the investigator 4. Preoperative imaging evaluation of the disease stage as AJCC TNM stage III and above non-M1 (among them, the preoperative imaging criteria for lymph node metastasis are: enhanced CT or MRI with enlarged lymph nodes, short diameter = 1.5cm or short diameter =1.0cm with enhanced manifestations; or PET-CT, PET-MR has high uptake) 5. No prior systemic anti-tumor therapy (radiotherapy, chemotherapy, targeted or immunotherapy, etc.) 6. Expected survival time> 3 months 7. At least 1 measurable lesion according to RECIST1.1 criteria 8. ECOG PS score of 0-1 9. Adequate organ function, subjects need to meet the following laboratory indicators: 1) Absolute neutrophil value (ANC) = 1.5x10^9/L and platelet = 90×10^9/L without granulocyte colony-stimulating factor in the past 14 days; 2) Hemoglobin > 9g/dL in the absence of blood transfusion or erythropoietin use in the past 21 days; 3) Total bilirubin =3× upper limit of normal (ULN); 4) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at = 2.5× ULN (patients with liver metastases are allowed ALT or AST =5×ULN); 5) Alkaline phosphatase (AKP) =2.5×ULN 6) creatinine clearance (calculated using the Cockcroft-Gault formula) = 50 ml/min; 7) good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) = 1.5 times ULN; 8) normal thyroid function, defined as thyroid-stimulating hormone (TSH=10) within the normal range; If there is no clinically significant thyroid dysfunction after thyroid hormone supplementation, they can also be enrolled. 9) Cardiac enzyme spectrum within the normal range (if the investigator comprehensively judges that it is not clinically significant, simple laboratory abnormalities are also allowed to enroll); 10. For female subjects of childbearing potential, a urine or serum pregnancy test with a negative result within 3 days prior to receiving the first dose of study drug (Cycle 1 Day 1). If a urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is requested. Females of non-childbearing potential are defined as at least 1 year postmenopausal, or have undergone surgical sterilization or hysterectomy. 11. If there is a risk of conception, all subjects, male or female, are required to use contraception with an annual failure rate of less than 1% throughout the treatment period and up to 120 days after the last dose of study drug.
Exclusion criteria
Exclusion criteria: 1.Diagnosed with other malignant diseases other than biliary tract within 5 years before the first administration (excluding cured skin basal cell carcinoma, skin squamous cell carcinoma, and/or carcinoma in situ after radical resection. Patients after radical resection of papillary thyroid carcinoma can also be enrolled). 2.Currently participating in an interventional clinical study treatment, or received other study drugs or used study devices for treatment within 4 weeks before the first administration. 3.Active autoimmune disease that required systemic treatment (such as using disease-modifying drugs, glucocorticoids or immunosuppressants) before the first administration. Replacement therapy (such as thyroxine, insulin or physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) is not considered systemic treatment. Known history of primary immunodeficiency. Patients with only positive autoimmune antibodies need to confirm whether there is autoimmune disease according to the investigator's judgment. 4.Currently or recently (within 10 days before receiving the first dose of study drug), continuous use of aspirin (>325mg/day) or other known non-steroidal anti-inflammatory drugs that can inhibit platelet function for 10 days. 5.Currently or recently (within 10 days before receiving the first dose of study drug), continuous use of full-dose oral or parenteral anticoagulants or thrombolytics for treatment. Note: Prophylactic use of low-dose anticoagulants is allowed: Under the premise that the international normalized ratio (INR) of prothrombin time is =1.5, prophylactic use of low-dose warfarin (=1mg/day), low-dose heparin (=12,000 U/day) or low-dose aspirin (=100mg/day) is allowed. 6.Have hereditary bleeding tendency or coagulation disorders, or history of thrombosis. 7.Receiving systemic glucocorticoid treatment (excluding intranasal inhalation or local glucocorticoids by other routes) or any other form of immunosuppressive therapy within 4 weeks before the first administration of the study. Note: Physiological doses of glucocorticoids (=10 mg/day of prednisone or equivalent drugs) are allowed. 8.There is clinically uncontrollable pleural effusion/ascites (patients who do not need to drain the effusion or who have no significant increase in the effusion after stopping drainage for 3 days can be enrolled). 9.Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation. 10.Known allergy to the study drugs sintilimab, gemcitabine hydrochloride for injection, or the active ingredients or excipients of tegafur gimeracil oteracil potassium capsules. 11.Before starting treatment, not fully recovered from toxicity and/or complications caused by any intervention (i.e., =grade 1 or reaching baseline, excluding fatigue or hair loss). 12.Known history of human immunodeficiency virus (HIV) infection (i.e., positive HIV 1/2 antibody). 13.Untreated active hepatitis B (defined as positive HBsAg and detection of HBV-DNA copy number greater than the upper limit of normal value of the laboratory of the research center). Note: Hepatitis B subjects who meet the following criteria can also be enrolled: 1).Before the first administration, the HBV viral load is <2.5×10^3 copies/ml (500 IU/ml), and the subject should receive anti-HBV treatment during the entire study treatment period. 2).For subjects with HBcAb (+), HBsAg (-), HBsAb (-) and HBV viral load less than the upper li
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1-year Relapse-free survival rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate;Disease control rate;Relapse-free survival;Overall survival;Clinical downstage rate;Major pathological response rate;pathological complete response rate;R0/R1 resection rate;safety; | — |
Countries
China
Contacts
Public ContactBin Yi
Shanghai Eastern Hepatobiliary Surgery Hospital
Outcome results
None listed