Toripalimab Plus Neoadjuvant Chemotherapy Combined With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This Phase II randomized study is to determine the efficacy and toxicity of toripalimab plus neoadjuvant chemotherapy combined with chemoradiotherapy for locally advanced unresectable esophageal squamous cell carcinoma.

Detailed Description
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This Phase II randomized study is to determine the efficacy and toxicity of toripalimab plus neoadjuvant chemotherapy combined with chemoradiotherapy for locally advanced unresectable esophageal squamous cell carcinoma. All patients were planned to receive 2 cycle of toripalimab plus paclitaxel/nedaplatin as neoadjuvant therapy. Then they all receive radical dose of chest radiation and concurrent chemotherapy of capecitabine (PO 1000 mg/m2, bid, d1-d14, q3w).

Official Title
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A Prospective Single-arm Phase Ⅱ Study of Toripalimab Plus Neoadjuvant Chemotherapy Combined With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Toripalimab
* Drug: Paclitaxel-albumin
* Drug: Nedaplatin
* Radiation: SMART
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed esophageal squamous cell carcinoma patients have measurable or evaluable lesions based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria unresectable T2-4 N0-3 M0 confirmed by CT or MRI ECOG performance status 0-1 no previous chest radiotherapy, immunotherapy or biotherapy. hemoglobin≥10 mg/dL, platelet≥100000/μL,absolute neutrophil count ≥1500/μL serum creatinine ≤1.25 times the upper normal limit(UNL), or creatinine clearance≥60 ml/min bilirubin ≤1.5 times UNL, AST（SGOT）≤2.5 times UNL ,ALT（SGPT）≤2.5 times UNL,alkaline phosphatase ≤5 times UNL FEV1 >0.8 L CB6 within normal limits patients and their family signed the informed consents Exclusion Criteria: previous or recent another malignancy, except for nonmelanoma skin cancer or cervical cancer in situ contraindication for chemotherapy women in pregnancy, lactation period, or no pregnancy test 14 days before the first dose women who has the probability of pregnancy without contraception tendency of hemorrhage in other clinical trials within 30 days addicted in drugs or alcohol, AIDS patients uncontrollable seizure or psychotic patients without self-control ability severe allergy or idiosyncrasy not suitable for this study judged by researchers

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: Toripalimab plus Paclitaxel/Nedaplatin followed by concurrent chemoradiotherapy<br>Patients in experimental group receive 2 cycles Toripalimab plus Paclitaxel/Nedaplatin, then followed by daily simultaneous modulated accelerated radiotherapy combined with Capecitabine. | Drug: Toripalimab<br>* Toripalimab 240 mg, d1, Q3w for two cycles<br>Drug: Paclitaxel-albumin<br>* Paclitaxel-albumin 260 mg/m2, d1, Q3w for two cycles<br>Drug: Nedaplatin<br>* Nedaplatin 75mg/m2, d1, Q3w for two cycles<br>Radiation: SMART<br>* Once-daily simultaneous modulated accelerated radiotherapy (PTV-GTV: 60Gy/24f )<br>Drug: Capecitabine<br>* Capecitabine 1000 mg/m2, bid, d1-14, q3w during radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year progression-free survival rate |  | 2-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year overall survival rate |  | 2-year | 
| Clinical response rate | the percentage of patients who had partial remission or complete remission after therapy | 2 months after radiotherapy | 
| the rate of grade 3 or 4 toxicities according to CTCAE4.0 | the percentage of patients who develop grade 3 or 4 toxicities | 1 year after therapy | 
| 2-year distant metastasis-free survival |  | 2-year | 
| 2-year locoregional recurrence-free survival |  | 2-year | 
| Quality of life assessed by QLQ-C30 |  | 2-year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Toripalimab, Neoadjuvant, Concurrent Chemoradiotherapy, Esophageal Squamous Cell Carcinoma