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The effect of neo-adjuvant immunochemotherapy on survival of patients with thoracic esophageal squamous cell carcinomas remains unknown. One of our objectives is to evaluate whether the neo-adjuvant immunochemotherapy Toripalimab (JS001) with cisplatin and paclitaxel followed by right thoracic approach esophagectomy with total 2-field lymph node dissection improves the overall survival of thoracic esophageal cancer patients versus neo-adjuvant chemotherapy.
The effect of immunochemotherapy in second line treatment of esophageal cancer got a positive results in the world. We tried to apply the immunotheray in resectable esophageal cancer and have planed this phase III clinical trials. The optimal management of resectable esophageal squamous cell carcinomas may have a new chapter in the era of immunotherapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Neoadjuvant immunochemotherapy | Experimental | Neo-adjuvant chemotherapy(cisplatin and paclitaxel): Paclitaxel, 175mg/m2, d1, Cisplatin, 75mg/m2, d1, 3 week, 2 cycles. JS001, 240mg ivgtt, d3, >30min, 3week, 2 cycles Surgery: 2-3weeks after Neo-adjuvant chemotherapy Surgeons: the operation shall be performed by senior thoracic surgeons. Try to achieve the consistency of operation quality. Operation: the thoracic esophagectomy must be through right thoracic cavity. (open and minimally invasive McKeown or Ivor Lewis). Total two-field lymphadenectomy (right and left recurrent laryngeal nerve lymph nodes must be included). After surgery/ maintain period: JS001, 240mg ivgtt, d3, >30min, 3week (8 cycles at most) |
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| Neoadjuvant chemotherapy | Active Comparator | Neo-adjuvant chemotherapy(cisplatin and paclitaxel): Paclitaxel, 175mg/m2, d1, Cisplatin, 75mg/m2, d1, 3 week, 2 cycles. Surgery: 2-3weeks after Neo-adjuvant chemotherapy Surgeons: the operation shall be performed by senior thoracic surgeons. Try to achieve the consistency of operation quality. Operation: the thoracic esophagectomy must be through right thoracic cavity. (open and minimally invasive McKeown or Ivor Lewis). Total two-field lymphadenectomy (right and left recurrent laryngeal nerve lymph nodes must be included). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Neoadjuvant immunochemotherapy | Drug | Neo-adjuvant chemotherapy(cisplatin and paclitaxel): Paclitaxel, 175mg/m2, d1, Cisplatin, 75mg/m2, d1, 3 week, 2 cycles. JS001, 240mg ivgtt, d3, >30min, 3week, 2 cycles Surgery: 2-3weeks after Neo-adjuvant chemotherapy Surgeons: the operation shall be performed by senior thoracic surgeons. Try to achieve the consistency of operation quality. Operation: the thoracic esophagectomy must be through right thoracic cavity. (open and minimally invasive McKeown or Ivor Lewis). Total two-field lymphadenectomy (right and left recurrent laryngeal nerve lymph nodes must be included). After surgery/ maintain period: JS001, 240mg ivgtt, d3, >30min, 3week (8 cycles at most) |
| Measure | Description | Time Frame |
|---|---|---|
| Event-free survival (EFS) | The date from the beginning of randomization to the date of first record of unresectable disease, distant metastases, local recurrences of any causes, and death of any cause. | The date from the beginning of randomization to the date of first record. 3 years EFS |
| Event-free survival (EFS) | The date from the beginning of randomization to the date of first record of unresectable disease, distant metastases, local recurrences of any causes, and death of any cause. | The date from the beginning of randomization to the date of first record. 5 years EFS |
| Measure | Description | Time Frame |
|---|---|---|
| pCR | pathological complete response rate | within 14 working days after operation |
| DFS | Disease free survival | 3 years DFS |
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Inclusion Criteria:
Exclusion Criteria:
1. Multiple primary cancer. 2.Patients with infections disease that require treatment 3.Patients who need continuous hormone treatment 4.unstable angina within 3 months, myocardial infarction within 6 months 5.psychopath 6.Patients with concomitant hemorrhagic disease. 7.Any unexpected reason for patients can't get operation 8.Inability to use gastric conduit after esophagectomy because of a prior surgery.
9.Pregnant or breast feeding 10.Patients are diagnosed or suspected to be allergic to cisplatin or Paclitaxel.
11.Bronchial asthma who requires intermittent use of bronchodilators or medical interventions 12.Due to co-existing diseases, the immunosuppressant was used. And the dosage of immunosuppressant was more than 10mg/ day orally and more than 2 weeks before enrollment 13.Abnormal coagulation function (PT>16s, APTT>53s, TT>21s, Fib<1.5g/L), tendency of bleeding or receiving thrombolysis or anticoagulant therapy 14.Previous or present pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, lung function severely impaired 15.Autoimmune diseases, immune deficiency, organ transplantation; 16.Hepatitis b/c patients。
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yan Zheng, PhD, MD | Contact | +86+15713660065 | sunnyzheng1@126.com | |
| Haibo Sun, PhD, MD | Contact | sunny-haipo@hotmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Yan Zheng, PhD, MD | Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Henan Cancer Hospital (The Affiliated Cancer Hospital of Zhengzhou University) | Recruiting | Zhengzhou | Henan | 450003 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33553366 | Derived | Zheng Y, Liu XB, Sun HB, Xu J, Shen S, Ba YF, Yan M, Qin Z, Liu BX, Wang ZF, Liu SL, Zhang RX, Chen PN, Liang GH, Yuan D, Li ZX, Liu Q, Wang HR, Li HM, Lv H, Ma X, Zhu J, Yu YK, Xing WQ; written on Henan Cancer Hospital Thoracic Oncology Group (HCHTOG). A phase III study on neoadjuvant chemotherapy versus neoadjuvant toripalimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: Henan Cancer Hospital Thoracic Oncology Group 1909 (HCHTOG1909). Ann Transl Med. 2021 Jan;9(1):73. doi: 10.21037/atm-20-5404. |
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| ID | Term |
|---|---|
| D004938 | Esophageal Neoplasms |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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|
| DFS | Disease free survival | 5 years DFS |
| OS | Overall survival rate | 3 years OS |
| OS | Overall survival rate | 5 years OS |
| ORR | The Overall Response Rate. ORR=CR+PR. Criteria: Response Evaluation Criteria in Solid Tumors, RECIST. | 3-4 weeks after the last cycle of neoadjuvant treatment |
| R0 resection rate | the complete resection rate of all tumor under microscope | within 14 working days after operation |
| MPR | MPR rate was defined as the percentage of patients who achieved a major pathological response (residual tumor ≤10%) | within 14 working days after operation |
| EORTC QLQ-C30 | EORTC QLQ-C30 repeated measurement model | before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation |
| EORTC QLQ-OES18 | EORTC QLQ-OES18 repeated measurement model | before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation |
| NRS-2002 | NRS-2002 repeated measurement model | before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation |
| D006258 |
| Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |