SOX Regimen as Neoadjuvant Chemotherapy for AJCC Stage II-III Gastric Cancer

Study Overview
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Brief Summary
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This is a randomized, multicenter, controlled trial to prove efficacy of S-1 and Oxaliplatin as Neoadjuvant Chemotherapy for Advanced Gastric Cancer Patients who undergo D2 gastrectomy. The primary endpoint is three-year free disease and the second primary includes five-year overall survival, safety and R0 resection rate.

Official Title
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Phase III, Randomized, Multicenter, Controlled Evaluation of S-1 and Oxaliplatin as Neoadjuvant Chemotherapy for Advanced Gastric Cancer Patients

Conditions
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Gastric Adenocarcinoma

Intervention / Treatment
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* Drug: Oxaliplatin+S-1
* Drug: Adjuvant Oxaliplatin/S-1（SOX）


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed gastric adenocarcinoma Gastroesophageal junction tumour type II or III(NCCN 2009) can be enrolled All patients must undergo EUS,CT(or PET-CT) and laparoscopy to evaluate tumor stage classification (TNM), and only stage II or III (AJCC 7th) gastric cancer patients can be enrolled planning to undergo gastric cancer D2 surgery after neoadjuvant chemotherapy KPS > 60; ECOG performance status 0-2 Life expectancy > 6 months Age: 20 to 75 years No other severe disease and life expectancy less than five years 7 days before enrolled, baseline data should be finished including: Granulocyte count ≥ 1.5×109/L; platelet count ≥ 100×109/L; Hemoglobin ≥ 90g/L; hepatic < 1.5×ULN; total bilirubin ≤ 1.0×ULN; creatinine < 1.5×ULN; PT-INR/PTT < 1.7× ULN Disease had to be measurable by the Response Evaluation Criteria in Solid Tumors (RECIST1.1) criteria Written informed consent and able to comply with the protocol Exclusion Criteria: Patient cannot undergo surgery or chemotherapy because of other severe disease Be allergic to chemotherapy drugs Patients receiving any chemotherapy or drugs involved in this trial in four weeks before enrolled Patients received cytotoxic chemotherapy, targeted therapy, immunotherapy or radiotherapy for gastric cancer Within the last 5 years in patients with a history of other malignant diseases Pregnant or breast-feeding women Severe heart disease like symptoms of coronary heart disease, New York Heart Association (NYHA) grade II or worse congestive heart failure or cardiac arrhythmia having medications or myocardial infarction within the last 12 months Patients with upper gastrointestinal obstruction or absorption anomaly; patient in obstruction of the Helicobacter pylori failure like effect S-1 to take and absorb Patients with a history of peripheral nerve disease Patients who get organ transplant lack of dihydropyrimidine dehydrogenase (DPD) Infection or other disease failure to control

Ages Eligible for Study
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Minimum Age: 20 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: Arm A:Neoadjuvant sox<br>Patients in arm a will receive (N=2-4) cycles of neoadjuvant SOX first, and then standard gastrectomy with D2 lymphadenectomy, and (8-N) cycles of adjuvant SOX adjuvant chemotherapy. | Drug: Oxaliplatin+S-1<br>* S-1: 40 60mg bid，po, d1 14 （S-1：BSA <1.25m2, 40mg bid, 1.25m2≤BSA≤1.5m2,50mg bid, BSA>1.5m2, 60mg bid） oxaliplatin：130mg/m2，iv drip for 2h，d1<br>* Other names: S-1(Taiho);|
| Active Comparator: Arm B:Adjuvant SOX<br>Patients in arm B will receive standard gastrectomy with D2 Lymphadenectomy first, and 8 cycles of adjuvant SOX later. | Drug: Adjuvant Oxaliplatin/S-1（SOX）<br>* S-1：40 60mg bid，d1 14 q3W oxaliplatin：130mg/m2，iv drip for 2h，d1,q3W 8 cycles (6 months)<br>* Other names: S-1(Taiho);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease free survival | SOX regimen as Neoadjuvant chemotherapy for AJCC II-III gastric cancer patients is superior than postoperative SOX after D2 surgery.Disease free survival is defined as time of surgery to recurrence or death. | three years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate | For neoadjuvant chemotherapy patients,response rate will be evaluated according to RECIST 1.1 criteria after at least 2 cycles of SOX chemotherapy.CT scan is required to every patient. | 3 months | 
| overall survival | Neoadjuvant chemotherapy of SOX is superior than postoperative SOX after D2 dissection in AJCC II-III gastric cancer patients.Overall survival is defined as the time of randomization to death. | five years | 
| safety | Number of participants with adverse events related to SOX chemotherapy.All adverse events are from CTCAE 4.0 criteria. | six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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two arms, D2 lymphadenectomy, chemotherapy before and after surgery, disease free survival