A Study of Sintilimab Plus Chemoradiation Before Surgery for Esophageal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to test the the efficacy and safety of sintilimab in combination with chemoradiation before surgery for esophageal cancer.

Official Title
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A Study of Anti-PD-1 Antibody, Sintilimab Plus Chemoradiation Before Surgery for Esophageal Cancer

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Biological: Sintilimab
* Drug: carboplatin/paclitaxel
* Radiation: Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed esophageal squamous carcinoma 18≤age≤75 ECOG PS is 0-1 TanyN+M0 or T3-4NanyM0 tumors Patients must have surgically resectable disease treatable by esophagectomy, as assessed by a thoracic surgeon No prior chemotherapy,radiotherapy and immunotherapy Disease must be clinically limited to the esophagus No esophageal perforation and no active esophageal bleeding No interstitial pneumonia or history of interstitial pneumonia FEV1>1.2L Adequate organ function defined at baseline as: WBC ≥3,000/ L，ANC ≥1,500/ L，Platelets ≥100,000/ L，Hb ≥9 g/dl； Calculated creatinine clearance >40 ml/min using Cockcroft-Gault method: Males: Creatinine CL = Weight (kg) x (140 - Age) . (mL/min) 72 x serum creatinine (mg/dL)Female：Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)；Total serum bilirubin ≤1.5 mg/dL， AST/ALT ≤2.5× upper limit of normal，Mean QT interval corrected for heart rate (QTc) <470 ms calculated from 3 ECGs using Frediricia's Correction Able to provide written informed consent Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up Exclusion Criteria: Previous treatment with chemotherapy, radiotherapy or immunotherapy Cervical esophageal cancer Esophageal perforation or active esophageal bleeding Interstitial pneumonia or history of interstitial pneumonia Patients with evidence of metastatic disease Chronic Hepatitis B or C infection (e.g. Hepatitis B surface Ag positive or detectable viral load for Hepatitis B or C). Patients with prior evidence of Hepatitis B or C without active infection are eligible Autoimmune diseases (such as systemic lupus erythematosus, rheumatoid rthritis, inflammatory bowel disease, autoimmune thyroid disease), but allow the following diseases to enter the next stage of screening: type I diabetes, skin diseases without systemic treatment (such as vitiligo, psoriasis) 14 days before the first dose, the patient had an active infection that required systemic treatment Inability to understand or may not comply with test requirements

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: arm<br>Biological: Sintilimab For weight <60kg, 3mg/kg IV Q3W day 1, and for weight≥60kg, 200mg IV Q3W day 1 Drug: Paclitaxel 50 mg/m^2 IV Q3W day 1, day 8 and day 15 Drug: carboplatin AUC: 2 IV Q3W day 1, day 8 and day 15 Radiotherapy: 1.8 Gy/fraction ×23 fractions Monday to Friday total dose of 41.4 Gy | Biological: Sintilimab<br>* Other Name: (IBI308)<br>Drug: carboplatin/paclitaxel<br>* carboplatin AUC 2/paclitaxel 50 mg/m2 weekly<br>Radiation: Radiation<br>* IMRT or VMAT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| unacceptable toxicity | Unacceptable toxicity is defined as any of the following toxicities: >1 episode of grade 3/4 neutropenia or thrombocytopenia <75,000/μL (despite prior dose reduction) during chemoradiation any toxicity that results in >2 week cumulative delay in chemoradiation any toxicity that is attributed to durvalumab which results in a delay of >8 weeks in surgery, i.e. surgery >16 weeks from the end of radiation, for a potentially operable patient any reason that is attributed to durvalumab which leads to death within 30 days of surgery | 1 year | 
| pathologic complete response rate, pCR |  | 1 year | 
| major pahological response, MPR |  | 1 year |