Combination of Gemcitabine, Oxaliplatin, Sintilimab and Bevacizumab in Unresectable Biliary Tract Cancer

Study Overview
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Brief Summary
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Study design: Prospective, single-arm, single-center phase II clinical study; Primary endpoint: Conversion rate; Secondary endpoints: Safety, disease control rate, disease-free survival, and overall survival; Main characteristics of enrolled patients: Patients with initially unresectable biliary tract cancer; Interventions: Combination of Gemcitabine, Oxaliplatin, Sintilimab and Bevacizumab; Sample size: 34 patients; Treatment until: 1. successfully conversed to resectable disease 2. progressed disease 3. intolerable toxicity 4. patient requests withdrawal; Research process: In this study, patients who met the inclusion criteria were evaluated at the end of every 3 weeks of treatment, up to surgical treatment or disease progression; Safety evaluation: Evaluate adverse reactions according to CTCAE 4.0; Follow up: 12 months after the last case was enrolled.

Official Title
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Efficacy and Safety of the Combination of Gemcitabine, Oxaliplatin, Sintilimab and Bevacizumab in Initially Unresectable Biliary Tract Cancer

Conditions
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Biliary Tract Carcinoma, Initially Unresectable

Intervention / Treatment
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* Drug: Combination of Gemcitabine, Oxaliplatin, Sintilimab and Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 and ≤80 years; ECOG 0 1; Histologically or cytologically confirmed carcinoma of the bile duct or gallbladder; Imaging assessment of disease stage III/IVA/any TN1M0*; The main organs have good functions and the examination indexes meet the following requirements: Blood routine test: Hemoglobin ≥90 g/L (no blood transfusion within 14 days); Neutrophils count ≥1.5×10^9/L; Platelet count ≥80×10^9/L; Biochemical tests: Total bilirubin ≤2×ULN (upper limit of normal value); Blood alanine aminotransferase (ALT) or blood aspartate aminotransferase (AST) ≤ 2.5×ULN; Endogenous creatinine clearance rate ≥ 50 mL /min (Cockcroft-Gault formula); Voluntarily signed the informed consent; Good compliance and family members are willing to cooperate with follow-up. Exclusion Criteria: Other uncured malignancies; Pregnant or lactating women, if the subject becomes pregnant during the study period, should withdraw from the clinical trial; Previous anti-tumor therapy for the disease in this study; Participated in other drug clinical trials within one month; Patients with known history of other systemic serious diseases before screening; Long-term unhealed wounds or incomplete healed fractures; Have a history of organ transplantation; Abnormal blood coagulation, with bleeding tendency (14 days before randomization must meet: INR within the normal range without the use of anticoagulants); Patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogs; The use of low-dose warfarin (1 mg orally, once daily) or low-dose aspirin (not more than 100 mg daily) for prophylactic purposes is permitted, provided that INR is less than 1.5; The incidence of arterial/venous thrombosis events in the previous year, such as cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis and pulmonary embolism, was screened; People with a history of psychotropic substance abuse and unable to get rid of it or with mental disorders; Have a history of immunodeficiency, or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation; 12. Concomitant diseases that, in the Investigator's judgment, seriously endanger patient safety or affect patient completion of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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>Combination of Gemcitabine, Oxaliplatin, Sintilimab and Bevacizumab Gemcitabine: 1000mg/m^2, iv, d1, d8, q3w Oxaliplatin: 100mg/m^2, iv, d1, q3w Sintilimab: 200mg, iv, d1, q3w Bevacizumab: 5mg/kg, d1, q3w | Drug: Combination of Gemcitabine, Oxaliplatin, Sintilimab and Bevacizumab<br>* Combination of Gemcitabine, Oxaliplatin, Sintilimab and Bevacizumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | objective response rate | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety：the incidence of adverse events and serious adverse events | Incidence of adverse events and serious adverse events | 3 weeks | 
| disease control rate | disease control rate | 3 weeks | 
| progress-free survival | progress-free survival | 3 weeks | 
| overall survival | overall survival | 3 weeks |