Neo-adjuvant Immunochemotheray Versus Neo-adjuvant Chemotherapy for Resectable Esophageal Carcinoma
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Neoadjuvant immunochemotherapy 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) |
Drug: Neoadjuvant immunochemotherapy
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)
|
| Active Comparator: Neoadjuvant chemotherapy 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). |
Drug: Neoadjuvant immunochemotherapy
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)
|
Outcome Measures
Primary Outcome Measures
- Event-free survival (EFS) [The date from the beginning of randomization to the date of first record. 3 years 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.
- Event-free survival (EFS) [The date from the beginning of randomization to the date of first record. 5 years 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.
Secondary Outcome Measures
- pCR [within 14 working days after operation]
pathological complete response rate
- DFS [3 years DFS]
Disease free survival
- DFS [5 years DFS]
Disease free survival
- OS [3 years OS]
Overall survival rate
- OS [5 years OS]
Overall survival rate
- ORR [3-4 weeks after the last cycle of neoadjuvant treatment]
The Overall Response Rate. ORR=CR+PR. Criteria: Response Evaluation Criteria in Solid Tumors, RECIST.
- R0 resection rate [within 14 working days after operation]
the complete resection rate of all tumor under microscope
- MPR [within 14 working days after operation]
MPR rate was defined as the percentage of patients who achieved a major pathological response (residual tumor ≤10%)
- EORTC QLQ-C30 [before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation]
EORTC QLQ-C30 repeated measurement model
- EORTC QLQ-OES18 [before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation]
EORTC QLQ-OES18 repeated measurement model
- NRS-2002 [before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation]
NRS-2002 repeated measurement model
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologic diagnosis of local advance squamous cell thoracic esophageal carcinoma of Stage (T1N1-3 or T2-3N0-3 M0), (8th Union for International Cancer Control, UICC-TNM).
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No metastatic lymph node in cervical by color doppler sonography.
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Patients must not have received any prior anticancer therapy of esophageal carcinoma.
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Age ranges from 18 to 75 years.
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Without operative contraindication.
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Absolute white blood cells count ≥4.0×109/L, neutrophil ≥1.5×109/L, platelets ≥100.0×109/L, hemoglobin ≥90g/L, and normal functions of liver and kidney, total bilirubin（TBIL）≤1.5N, aspartate aminotransferase (AST)≤2.5N, alanine aminotransferase(ALT)≤2.5N, prothrombin time(PT)≤1.5N, and activated partial thromboplastin time(APTT) is in normal range, endogenous creatinine clearance rate(CRE)≤1.5N.
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Patients must not have diagnosed with other cancer and must not received any prior anticancer therapy except prostatic cancer with more than 5 years disease-free survival(DFS).
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expected R0 resection.
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ECOG 0～1.
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Patients should agree to use contraceptive measures during the study period and within 6 months of the end of the study. Women must be non-lactation.
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Signed informed consent document on file. 10. .
Exclusion Criteria:
-
- 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。
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Henan Cancer Hospital (The Affiliated Cancer Hospital of Zhengzhou University) | Zhengzhou | Henan | China | 450003 |
Sponsors and Collaborators
- Henan Cancer Hospital
Investigators
- Principal Investigator: Yan Zheng, PhD, MD, Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HCHTOG1909