Sintilimab and Chemotherapy Sequential Radiotherapy in Advanced Esophageal Cancer

Study Overview
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Brief Summary
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This is an investigator-initiated, single-arm, exploratory clinical study.The study population consisted of treatment naive advanced esophageal squamous cell carcinoma patients. The purpose of this study was to evaluate the efficacy and safety of immunotherapy combined with chemotherapy and residual lesions irradiation of esophageal squamous cell carcinoma.

Official Title
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The Prospective Study of Sintilimab Combination With Chemotherapy Sequential Radiotherapy for Advanced Esophageal Squamous Cell Carcinoma

Conditions
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Metastatic Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: TP regimen (cis-platinum ; Tocetaxel ) combined with PD-1 inhibitors（Sintilimab）


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with Stage IV esophagus squamous cell carcinoma. Expected survival time ≥3 months Enrolled patients must have at least one measurable lesion conforming to the RECIST V1.1 definition. Physical fitness ECOG score of 0 or 1 Organ function levels must meet the following requirements and meet the following standards: A) Bone marrow function: absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet count ≥90×10^9/L, hemoglobin ≥90 g/L; B) Liver function: Total bilirubin TBIL≤1.5×ULN (total bilirubin ≤3×ULN in Subjects with Gilbert's syndrome, liver cancer or liver metastasis), AST and ALT ≤2.5×ULN in patients without liver metastasis, AST and ALT ≤5.0×ULN in patients with liver metastasis; C) Renal function: Creatinine (Cr) ≤1.5×ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to Cockcroft and Gault formula); D) Urine routine / 24-hour protein quantification: qualitative urine protein ≤1+ (if qualitative urine protein ≥2+, 24 hours < 1g can be included); E) Cardiac function: left ventricular ejection fraction ≥50%; F) Coagulation function: International standardized ratio (INR) ≤1.5×ULN, and activated partial thrombin time (APTT) ≤1.5×ULN; Exclusion Criteria: Known or suspected history of active autoimmune diseases, autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, pituitaritis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes) Have a history of immunodeficiency, including HIV positive, or other acquired, congenital immunodeficiency disease, or history of organ transplantation and bone marrow transplantation；Interstitial lung disease, drug-induced pneumonia,requiring steroid therapy or active pneumonia with clinical symptoms or severe pulmonary dysfunction； There are clinical symptoms or diseases of the heart that are not well controlled, such as: (1) heart failure of NYHA class 2 or higher (2) unstable angina (3) myocardial infarction within 24 weeks (4) clinical need for treatment or Interventional supraventricular or ventricular arrhythmia； Have a tendency to hereditary bleeding or coagulopathy. Clinically significant bleeding symptoms or clear bleeding tendency within 3 months prior to enrollment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood++ and above； Allergic reactions to test drugs for this application； Pregnant or lactating women； Those whom the investigator considered unsuitable for inclusion。

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 chemo-immuno-irradiation<br>TP regimen plus PD-1 inhibitor for 4 cycles then irradiation and PD-1 inhibitor maintenance therapy for 13 cycles. | Drug: TP regimen (cis-platinum ; Tocetaxel ) combined with PD-1 inhibitors（Sintilimab）<br>* TP regimen (cis-platinum ; Tocetaxel ) combined with PD-1 inhibitors（Sintilimab）for 4 cycles, then irradiation of the residual lesions for 50Gy/2Gy/25f. After complete irradiation, sintilimab is administered every 21 days a cycle for additional 13 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | overall survival | up to 24 months | 
| PFS | progression-free survival | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate | ORR | up to 12 weeks | 
| toxicities | toxicities | up to 12 weeks |