Combination of Chemotherapy Plus RT and SHR-1210 to Treat Patients With ESCC

Study Overview
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Brief Summary
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SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody. This is an openlabel，single center ，non-randomized ，Single Arm Exploratory Study . This clinical study is an investigator-initiated clinical trial（IIT). The objective of this study is to evaluate the efficacy and safety of radiation therapy combined with anti-PD-1 antibody SHR-1210 and chemotherapy in patients with Locally Advanced Esophageal Squamous Cell Carcinomas。

Official Title
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A Single Arm Exploratory Study of Chemotherapy Plus Radiation Therapy and Anti-PD-1 Antibody SHR-1210 in Treating Patients With Locally Advanced Esophageal Squamous Cell Carcinomas

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: SHR-1210
* Radiation: IMRT or VMAT
* Drug: Apatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age:18-75 years, male or female. Histologically confirmed primary Squamous Cell Carcinoma of the Esophagus,Local advanced esophageal cancer diagnosed by pathology and imaging,clinical stage T3-4N0M0, T1-4N+M0,Ⅱ-Ⅳa. Pre-treatment evaluation can not tolerate concurrent radiochemotherapy or rejection of the concurrent use of chemotherapy with radiotherapy. Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. ECOG 0-1. Adequate organ function. Life expectancy of greater than 6 months. Patient has given written informed consent. Exclusion Criteria: Patients who have or are currently undergoing additional chemotherapy, radiation therapy, targeted therapy or immunotherapy. Known history of hypersensitivity to macromolecular protein preparation or any components of the SHR- 1210 formulation. Subjects before or at the same time with other malignant tumors (except which has cured skin basal cell carcinoma and cervical carcinoma in situ); Subjects with any active autoimmune disease or history of autoimmune disease - Page 4 of 4 [DRAFT] - Uncontrolled clinically significant heart disease, including but not limited to the following: (1) > NYHA II congestive heart failure; (2) unstable angina, (3) myocardial infarction within the past 1 year; (4) clinically significant supraventricular arrhythmia or ventricular arrhythmia requirement for treatment or intervention; Active infection or an unexplained fever > 38.5°C during screening or before the first scheduled day of dosing (subjects with tumor fever may be enrolled at the discretion of the investigator); Received a live vaccine within 4 weeks of the first dose of study medication. Pregnancy or breast feeding. Decision of unsuitableness by principal investigator or physician-incharge.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: SHR-1210 + Chemotherapy + Radiotherapy<br>Radiotherapy(IMRT or VMAT): 95%PTV 54Gy/30 fraction,95%PTV 60Gy/30 fraction ,5 fractions per week, for 6 weeks. Radiation begun the day on which first dose of SHR-1210. SHR-1210 (200mg fixed dose every 2 weeks, one cycle is four weeks, total 8 cycles ) will be administered as an intravenous infusion over 30 minutes. Chemotherapy: Docetaxel 25mg/m2/w, intravenous infusion on days 1, 8, 15, 22, total 4 cycles; Cisplatin 25mg/m2/w, intravenous infusion on days 1, 8, 15, 22;, total 4 cycles. Apatinib: 250mg/d，PO Qd(4 weeks after Radiotherapy, until the end of 8th ycle ) | Drug: SHR-1210<br>* SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody.<br>* Other names: Anti-PD-1 Antibody;Radiation: IMRT or VMAT<br>* The IMRT or VMAT technique was used in our study.<br>Drug: Apatinib<br>* Apatinib is a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AE), Serious Adverse Event(SAE) Adverse events | Incidence of Treatment-Emergent Adverse Events | Through study completion, an average of half a year] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Objective Response Rate | Through study completion, an average of 1 year | 
| PFS | Progression-Free Survival | 1year and 3years | 
| OS | overall survival | 1year and 3years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophageal Cancer, Concurrent chemoradiation, Immunotherapy, SHR-1210, Apatinib