Capecitabine Combined With Lenvatinib and Tislelizumab as Adjuvant Treatment After Resection in Patients With BTC

Study Overview
=================
Brief Summary
-----------------
This is a prospective, open-label, single-center clinical study, to evaluate the efficacy and safety of Capecitabine combined with Lenvatinib and Tislelizumab as adjuvant treatment after resection in patients with biliary tract cancer.

Official Title
-----------------
Capecitabine Combined With Lenvatinib and Tislelizumab as Adjuvant Treatment After Resection in Patients With Biliary Tract Cancer: A Single-arm, Phase II Study

Conditions
-----------------
Biliary Tract Cancer

Intervention / Treatment
-----------------
* Drug: Capecitabine combined with lenvatinib and tislelizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ages 18 and above Pathological reported showed Biliary tract cancer (include intrahepatic cholangiocarcinoma (IHCC), extrahepatic/hilar cholangiocarcinoma, muscle infiltrated gallbladder carcinoma or distal cholangiocarcinoma)，patients received R0 resection(including liver resection, pancreatectomy, or both). ECOG PS 0-1 Patients can tolerate the combination therapy and survive longer than 6 months. Organ function(Exclude use blood components and cell growth factors for 14 days): Neutrophils (ANC) ≥1,500/mm3, Platelet count (PLT)≥100,000/mm3, Hemoglobin (Hb) ≥9g/dL; Serum creatinine(SCR) ≤1.5*upper limit of normal(ULN),or creatinine clearance rate≥50 ml/min(Cockcroft-Gault Formula),Total bilirubin(TBIL)≤ 2*ULN,Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 3*ULN, urine protein≤2+(if urine protein≥2+, 24-hour urinary protein quantity must ≤1g), Adequate surgical biliary drainage and no infection signal. The coagulation function was normal (without active bleeding and thrombotic disease): International normalized ratio(INR)≤1.5*ULN, activated partial thromboplastin time(APTT)≤1.5×ULN, prothrombin time(PT)≤1.5*ULN. Women without surgical sterilization or childbearing age who are required to use a medically approved contraceptive method (such as an intrauterine device, birth control pill or condom) during the study period and for 3 months after the study period; Women are of reproductive age and not undergoing surgical sterilization whose the serum or urine HCG test must be negative within 7 days prior to study enrollment and must be non lactation period. Male patients without surgical sterilization or reproductive age are required to consent with their spouse to use a medically approved contraceptive method during the study treatment period and for 3 months after the study treatment period. The patients are voluntarily enrolled in the study, with good compliance and coordinate the follow-up for safety and survival Exclusion Criteria: Patients with pancreatic/ampullary carcinoma Patients with mucous gallbladder carcinoma Patients who had received radiotherapy or chemotherapy previously Incomplete surgery recovery or biliary obstruction exist Patients with radiographs confirmed distant metastases Patients with prior or concurrent malignancy(excluded Cured basal cell carcinoma of the skin and Carcinoma in situ elsewhere) Patients are allergy to macromolecular protein preparation(including anti-PD-1 antibody, uracil, cytosine pharmaceutical ingredients) There are significant factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction Patients had any active autoimmune disease or had experience of autoimmune disease. Patients are receiving immunosuppressant and continue using within 2 weeks before enrollment Patients with ascites or pleural effusion requiring therapeutic puncture or drainage Patients with disease of the heart that are not well controlled Abnormal coagulation(have tendency to bleed or receiving thrombolytic or anticoagulant therapy) Patients had active infection or unexplained fever during screening and before first dose Patients had abdominal fistula, gastrointestinal perforation, or abdominal abscess less than 4 weeks before first dose. Patients past or present with pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severely impaired lung function, etc Patients have congenital or acquired immune deficiency; Hepatitis B patients: HBV DNA≥10^3/ml, Hepatitis C patients: HCV RNA≥10^3/ml, Chronic hepatitis B virus carriers: HBV DNA<2000 IU/ml（<10^4 copies/ml), patients must receive antiviral therapy during the trial Patients are participating in other relevant clinical studies or it has been less than 1 month since the end of the previous clinical study; Patients maybe receive other systemic antitumor therapy during the study period; Patients received live vaccination less than 4 weeks before administration or possibly receive during the study period. Patients had history of psychotropic substance abuse, alcohol abuse, or drug abuse. Patients cannot or does not agree to pay the cost of examination and treatment expense The researchers concluded the patients should be excluded from this study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: combined treatment group<br>Capecitabine combined with lenvatinib and tislelizumab: Lenvatinib,8mg po. qd.Tislelizumab,200mg iv. q3w. Capecitabine 1250mg/m^2 bid.d1-d14 q3w | Drug: Capecitabine combined with lenvatinib and tislelizumab<br>* Capecitabine combined with lenvatinib and tislelizumab<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1 year DFS rate | one year disease free survival rate | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2 years DFS rate | two years disease free survival rate | 24 month | 
| 1 year OS rate | one year overall survival rate | 12 month | 
| 3 years OS rate | three years overall survival rate | 36 month | 
| AE | adverse event | 30 days from the beginning of treatment to the last treatment |