A Study of the Efficacy and Safety of Chemotherapy Combined With Toripalimab in Advanced Biliary Tract Cancer
Condition: Biliary Tract Cancer
MeSH terms: Biliary Tract Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      1. Target population: patients with advanced biliary tract cancer (including gallbladder
           carcinoma, intrahepatic and extrahepatic cholangiocarcinoma) .

        2. Primary objective: progression free survival (PFS)/ overall survival (OS) of first-line
           chemotherapy plus PD-1 antibody (Toripalimab) in patients with advanced biliary tract
           cancer.

      Secondary objectives:

        1. objective response rate (ORR) of first-line chemotherapy plus PD-1 antibody
           (Toripalimab)

        2. safety of first-line chemotherapy plus PD-1 antibody (Toripalimab)

      3.Trial design: This is a monocenter, single arm, phase II study to evaluate the efficacy and
      safety of first-line chemotherapy plus PD-1 antibody (Toripalimab) in patients with advanced
      advanced biliary tract cancer.

      4.Treatment plan: Patients will be given treatment as below once recruited: PD-1 antibody
      Toripalimab（240mg, iv, q3w），combined with GS regimen(gemcitabine 1000mg／m2 ，d1,d8 + S1
      40-60mg bid*14d，Q21d).

      The treatment will be continued until emerging of disease progression or intolerable adverse
      effects (The upper time limit for treatment is 2 years).

      5.Number of subjects: 40 patients. Number of centers: 1 sites ( Fudan University Affiliated
      Zhongshan Hospital).
    

Detailed description: 
      Backgrounds:

      Toripalimab (JS-001) is a PD-1 antibody developed by Shanghai Jun Shi Biomedical technology
      Co. Ltd. Nowadays, eighteen clinical trials of this drug have been conducted in patients with
      different types of advanced malignant tumor. Until now, Toripalimab has exhibited favorable
      safety in recruited patients. Incidence rate of SAE is 14.7%. JS001-Ib-CRP-1.0 is a phase
      Ib/II basket trial, aiming at evaluating safety and efficacy of JS001 in treating advanced
      gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma and head
      and neck squamous cell carcinoma.The interim analyses results of 161 patients show that the
      ORR is 22.4%.

      Now, the standard chemotherapies regimen for advanced biliary tract cancer include
      gemcitabine, platinum and fluorouracil; Considering the synergistic effect of chemotherapy
      and immune therapy, the investigators choose GS regimen (gemcitabine+S1) to combine
      Toripalimab.

      the investigators will shut down the study in advance, if unpredicted SAE or low efficacy
      occur.

      Patients with abnormal autoimmune status, unfavorable body function, factors impeding drug
      taking, absorption and metabolism will be excluded. Study participants with disease
      progression or severe/ intolerant toxicity during treatment will withdraw the study.

      Hyper-progressive disease is defined as 1) progression 2) more than doubled growth rate 3)
      tumor volume increase >50% in 2 months after initialing the treatment.
    

Intervention name(s): GS+Toripalimab
Intervention type(s): Drug
Intervention description(s): Patients will be given treatment as below once recruited: PD-1 antibody Toripalimab（240mg, iv, q3w），combined with GS regimen(gemcitabine 1000mg／m2 ，d1,d8 + S1 40-60mg bid*14d，Q21d).
The treatment will be continued until emerging of disease progression or intolerable adverse effects (The upper time limit for treatment is 2 years).
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Advanced Biliary Tract Cancer; PD-1 antibody(Toripalimab); first-line chemotherapy