Study of SHR-1210 in Combination With Chemotherapy in Advanced Esophageal Cancer

Study Overview
=================
Brief Summary
-----------------
This is a randomised, double-blinded, placebo-controlled, multi-center phase III trial, comparing the efficacy and safety of SHR-1210 + paclitaxel + cisplatin vs placebo+paclitaxel +cisplatin as 1L therapy for advanced esophageal cancer patients in China. SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody.

Detailed Description
-----------------
In this study, eligible subjects will be randomized into study arm or control arm. Treatment cycles of chemotherapy will be at most 6 cycles which would be decided by the investigators. Progression-free survival (PFS) assessed by the Independent Review Committee (IRC) and overall survival (OS) will be the primary outcomes.

Official Title
-----------------
PD-1 Antibody SHR-1210 Combined With Paclitaxel and Cisplatin Versus Placebo Combined With Paclitaxel and Cisplatin as First-line Therapy for Advanced Esophageal Cancer: a Randomized, Double-blinded, Controlled, Multi-center Phase III Trial

Conditions
-----------------
Advanced Esophageal Cancer

Intervention / Treatment
-----------------
* Drug: SHR-1210
* Drug: Placebo
* Drug: paclitaxel
* Drug: cisplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed unresectable local advanced/recurrent or metastasis esophageal squamous cell carcinoma; No previous systemic anti-tumor treatment; Subjects must have at least one measurable tumor lesion per RECIST 1.1; Tissue samples should be provided for biomarkers (such as PD-L1) analysis; ECOG: 0-1; Adequate organ and bone marrow function; Exclusion Criteria: Allergic to monoclonal antibodies, any SHR-1210 components, paclitaxel, cisplatin and other platinum drugs; Prior therapy as follow: Anti-PD-1 or anti-PD-L1; Any experimental drugs within 4 weeks of the first dose of study medication; Received major operations or serious injuries within 4 weeks of the first dose of study medication; Received last dose of anticancer therapy (including chemotherapy, radiotherapy, targeted therapy, etc.) within 4 weeks of the first dose of study medication; Not recovered to ≤CTCAE 1 from adverse events (except for hair loss) due to a previously anti-tumor treatment; Subjects with any active autoimmune disease or history of autoimmune disease; Pregnancy or breast feeding;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1210 + paclitaxel + cisplatin<br>Paclitaxel 175mg/m2, Day 1，cisplatin 75mg/m2，Day 1，SHR-1210 200mg，Day 2，every 3 weeks, maximum 6 cycles, then SHR-1210 maintenance | Drug: SHR-1210<br>* SHR-1210 200mg<br>* Other names: camrelizumab;Drug: paclitaxel<br>* paclitaxel 175mg/m2<br>Drug: cisplatin<br>* cisplatin 75mg/m2<br>|
| Active Comparator: placebo+paclitaxel + cisplatin<br>Paclitaxel 175mg/m2, Day 1，cisplatin 75mg/m2，Day 1，placebo，Day 2，every 3 weeks, maximum 6 cycles, then placebo maintenance | Drug: Placebo<br>* Placebo<br>Drug: paclitaxel<br>* paclitaxel 175mg/m2<br>Drug: cisplatin<br>* cisplatin 75mg/m2<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS assessed by IRC | based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1) | approximately 22 months | 
| OS | OS is defined as the time from registration to death due to any cause, or censored at date last known alive. Measured by the method of Kaplan and Meier. | approximately 22 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS assessed by investigators | based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1) | approximately 22 months | 
| 6 and 9 month OS rate | OS is defined as the time from registration to death due to any cause, or censored at date last known alive. Measured by the method of Kaplan and Meier. | approximately 6 and 9 months | 
| ORR | based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1) | approximately 22 months | 
| DCR | based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1) | approximately 22 months | 
| DoR | based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1) | approximately 22 months | 
| AE | adverse events | approximately 22 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PD-1Antibody, advanced esophageal cancer, paclitaxel, cisplatin