Neoadjuvant Therapy With Nab-paclitaxel and Cisplatin for Locally Advanced Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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To verify the role of nab-paclitaxel in neoadjuvant therapy for esophageal squamous cell carcinoma, the investigators designed a prospective, randomized, controlled , multicente phase II trial, to investigate the efficacy and safety of nab-paclitaxel combined with cisplatin as neoadjuvant therapy followed by surgery versus surgery alone for esophageal squamous cell carcinoma.

Official Title
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The Effectiveness and Safety of Neoadjuvant Therapy With Nab-paclitaxel and Cisplatin Followed by Surgery Versus Surgery Alone for Locally Advanced Esophageal Squamous Cell Carcinoma

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Nab-paclitaxel and Cisplatin
* Procedure: surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ranges from 18 to 75 years Radiographically, histologically or/and cytologically diagnosed resectable locally advanced middle-lower esophageal squamous cell carcinoma without distant metastasis,cT1N1M0 or T2-3N0-1M0(according to UICC esophageal cancer TNM staging system 8th edition) Enhanced CT showed the presence of potentially resectable lesions. Resectability features included no evidence of mediastinal infiltration, No evidence of tracheobronchial fistula or tumor entry into the airway Have not previously received systemic antitumor therapy for esophageal squamous cell carcinoma (Including radiotherapy, chemotherapy, targeted therapy, immunotherapy) ECOG performance status 0-1 Expected survival more than 6 months No contraindications in the organ function tests before surgery The laboratory test meet the following requirements: Bone marrow function: neutrophils ≥ 1.5×10(9)/L, platelets ≥ 100×10(9)/L, hemoglobin ≥ 90 g/L Liver function：Total bilirubin ≤ 1.5x ULN；AST and ALT) ≤ 2.5x ULN Renal function：Cr ≤ 1.5x ULN，Ccr ≥ 55 ml/min Coagulation function：INR≤1.5×ULN, PT≤1.5ULN, APTT within the normal range Female patients of child-bearing age agree to take effective contraceptive measures during the study period and 6 months after reseach completion；Pregnancy tests in serum or urine must be negative 7 days prior to study enrollment；Non-lactating patients；male patients agree to take effective contraceptive measures during the study period and 6 months after reseach completion Not concomitant with other uncontrollable benign disease before the recruitment(e.g. the infection in the kidney, lung and liver) Not participating in other clinical trials 4 weeks before the treatment The patient has good compliance with the planned treatment, understands the research process of the study and signs a written informed consent form. Exclusion Criteria: Histological confirmation of esophageal adenocarcinoma with distant metastasis, without radical resection (stage IV) Ever administrated with other drugs(including TCM drugs) before the recruitment, or no guarantee of progress according to the study requirement after recruitment Grade 2 or above peripheral neuropathy or hemorrhage according to NCI CTCAE 4.03 Combined with severe cardiovascular disease, including hypertension that cannot be controlled by medical treatment(BP≥160/95mmHg), unstable angina, a history of myocardial infarction in the past 6 months,Congestive heart failure>NYHA grade II, severe arrhythmia, pericardial effusion, etc. Combined with severe ADH abnormal secretion syndrome, poorly controlled diabetes: more than 40 units of insulin per day need to be continuously administered; or 40 units of insulin per day for continuous use or not used, but fasting blood glucose is still above 14mmol / L, HbA1c above 9.0 Long-term use of anticoagulants or vitamin K antagonists such as warfarin, heparin or its analogues for more than 6 months,small doses of warfarin (≤1mg / day) or aspirin (≤100mg / day) for prevention purposes are not included Major surgery within 4 weeks prior to enrollment, or surgical wounds have not fully healed Operation can not use the stomach instead of esophageal cancer to reconstruct the digestive tract due to previous operation Severe infection within 1 week prior to the start of study, requiring intravenous antibiotics, antifungal or antiviral therapy Known to be allergic, highly sensitive or intolerable to research-related drugs or excipient In the past 5 years, there were other malignant tumors, melanoma skin cancer or ervical carcinoma in situ were excepted Any indicator shows chemotherapy and surgery contraindications Women who are pregnant or lactating The investigator determined that unable to complete the study due to medical, social, or psychological reasons or were unable to sign valid informed consent

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neo-adjuvant chemotherapy group<br>cisplatin and nab-paclitaxel: Nab-paclitaxel, 125mg/m(2), d1,d8, Cisplatin, 75mg/m(2), d1, 3 week, 2 cycles. Surgery: 4-6weeks after Neo-adjuvant chemotherapy | Drug: Nab-paclitaxel and Cisplatin<br>* Nab-paclitaxel,125mg/m(2), d1,d8, Cisplatin,75mg/m(2), d1, 3 week, 2 cycles.<br>Procedure: surgery<br>* surgery<br>|
| Active Comparator: Surgery alone<br>Surgery alone | Procedure: surgery<br>* surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall survival，From date of randomization until death due to any cause | up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS rate | Overall survival rate | 1 year,3years,5years | 
| DFS rate | Disease free survival rate | 1 year,3years,5years | 
| R0 resection rate | R0 resection rate | within 4 weeks following the operation | 
| Down-staging rate | Down-staging rate | within 6 weeks following the last dose of chemotherapy | 
| Rate of Operative Complications |  | within 4 weeks following the operation | 
| Rate of Adverse Event | Incidence of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 | up to 6 weeks after the last dose of chemotherapy |