Toripalimab Combined With Gemcitabine/5--fluoropyrimidine for Advanced Cholangiocarcinoma

Study Overview
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Brief Summary
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The study is a phase II clinical trial of single arm. The purpose is to evaluate the safety and efficacy of anti-PD-1 antibody Toripalimab combined with chemotherapy(gemcitabine+5-fluorine pyrimidine) in unresectable advanced cholangiocarcinoma patients.

Official Title
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Clinical Study of Toripalimab Monoclonal Antibody Combined With Gemcitabine/5--fluoropyrimidine in the Treatment of Advanced Cholangiocarcinoma

Conditions
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Advanced Cholangiocarcinoma

Intervention / Treatment
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* Drug: Toripalimab
* Drug: Gemcitabine
* Drug: 5- fluorine pyrimidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically or cytologically confirmed cholangiocarcinoma stage IV disease,no system therapy for advanced disease one or more lesions that can be measured by imaging assessment 18 to 70 years of age and life expectancy exceeds 3 months adequate specimens for detection of PD-1/PD-L1 and MMR karnofsky performance status(KPS) score ≥70% routine blood routine, liver and kidney function and electrocardiogram were basically normal without contraindication of chemotherapy. Exclusion Criteria: dual cancers other than cholangiocarcinoma metastasis of central nervous system unreleased biliary obstruction acute infections requiring treatment non-infectious pneumonia requires glucocorticoid therapy, active autoimmune diseases, or systemic immunosuppressive therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: All patients were given Toripalimab 3 mg/kg (day 1 and 15); Gem+5-FU (Gem 1250mg/m2+CF 200 mg/m2+5-FU400 mg/m2 intravenous drip+5-FU 2.4-3.6 g/m2 continuous intravenous drip for 48 hours), the first and fifteenth days, four weeks for a cycle, a total of four cycles. After 4 cycles, Toripalimab was maintained at 3 mg/kg Q3 w for a total of 1 year if the disease was not progressing or toxic side effects were tolerated.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Toripalimab combined with Gem/5-FU<br>All patients were given Toripalimab 3 mg/kg (day 1 and 15); Gem+5-FU (Gem 1250mg/m2+CF 200 mg/m2+5-FU400 mg/m2 intravenous drip+5-FU 2.4-3.6 g/m2 continuous intravenous drip for 48 hours), the first and fifteenth days, four weeks for a cycle, a total of four cycles.After 4 cycles, Toripalimab was maintained at 3 mg/kg Q3 w for a total of 1 year if the disease was not progressing or toxic side effects were tolerated. | Drug: Toripalimab<br>* 3mg/kg on d1 and d15 q4W*4cycles，then 3mg/kg q3w for 1 year in total<br>Drug: Gemcitabine<br>* 1250mg/m2 on d1 and d15 q4W*4cycles<br>* Other names: Gem;Drug: 5- fluorine pyrimidine<br>* 400mg/m2 intravenous injection plus 5-FU 2.4g-3.6g/m2 continuous intravenous drip for 48h on d1 and d15 q4W*4cycles<br>* Other names: 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-month PFS rate | the rate of 6-month progression free survival | 6-month after the beginning of first line systemic therapy | 
| mPFS | the median of progression free survival | from the beginning of the first line systemic therapy until the date of first documented progression or date of death from any cause,whichever came first,assessed up to 24 months | 
| Toxic side effects | assess according to the National Cancer Institute-Common Terminology Criteria for Adverse Events 3.0 | from the beginning of the first line systemic therapy until the end of follow-up,assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | the objective response rate | from the beginning of the first line systemic therapy until the date of completion of therapy,assessed up to 13 months | 
| DCR | the disease control rate | from the beginning of the first line systemic therapy until the date of completion of therapy,assessed up to 13 months | 
| 1-year OS rate | the rate of 1-year overall survival | 1 year after the beginning of the first line systemic therapy | 
| mOS | the median of overall survival | from the beginning of the first line systemic therapy until the date of death from any cause,assessed up to 24 months |