A Comparison of Laparoscopic With Open Distal Gastrectomy in Advanced Gastric Cancer After Neoadjuvant Chemotherapy

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety and efficacy of laparoscopic distal D2 gastrectomy (LDG) compared with open surgery (ODG) for resectable gastric cancer, to determine whether LDG can be a test arm for a future Phase III trial to evaluate the non-inferiority of overall survival compared with ODG in patients who receive neoadjuvant chemotherapy.

Detailed Description
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The study is an open-label, controlled, randomized Phase II clinical trial. The protocol has been approved by the Ethics Committee of Beijing Cancer Hospital. The primary endpoint is the 3-year progression-free survival (PFS) rate. The secondary endpoints are the overall survival, surgical morbidity and mortality.

Official Title
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A Randomized, Single Center, Controlled Phase II Study to Compare Laparoscopic Versus Open Distal Gastrectomy in Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Neoadjuvant Chemotherapy
* Procedure: Laparoscopic gastrectomy
* Procedure: Open gastrectomy
* Drug: Adjuvant Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven adenocarcinoma of the stomach. Clinical cT2N+M0,or cT3-4a/N+M0 disease, confirmed by upper gastrointestinal endoscopy and abdominal computed tomography (CT) and laparoscopy. The T and N stages are determined by the method of Habermann et al. The gastric tumors are located in the middle to lower third of the stomach, are macroscopically resectable by distal gastrectomy with D2 lymph node dissection, and R0 or R1 resection can be achieved. No bulky lymph node metastasis is detected by abdominal CT. No pleural effusion, no ascites exceeding the pelvis and no metastasis to the peritoneum, liver or other distant organs are confirmed by abdominal pelvic CT. No clinically apparent distant metastasis. Karnofsky performance status ≥70%. Sufficient oral intake. No previous treatment with chemotherapy or radiation therapy for any tumors. No previous surgery for the present disease. Sufficient organ function, as evaluated by laboratory tests 7 days or more after the date when the anticancer drugs were given. When patients are recovering from myelosuppression,the revised criteria are shown in parentheses. White blood cell count≥3000/mm3 (2000/mm3) Platelet count≥10.0*104/mm3 (5.0*104/mm3) Aspartate aminotransferase≤100 IU/l Alanine aminotransferase≤100 IU/l Total bilirubin≤2.0 mg/dl Serum creatinine≤1.5 mg/dl No need for emergency surgery due to bleeding or perforation of the primary tumor. No mechanical obstruction. Written informed consent. Exclusion Criteria: Past history of upper abdominal surgery. Past history of surgery for the gastrointestinal tract. Body mass index exceeding 30 kg/m2.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Laparoscopic gastrectomy<br>Laparoscopic distal gastrectomy and D2 lymph node dissection are performed for locally advanced gastric cancer after neoadjuvant chemotherapy. | Drug: Neoadjuvant Chemotherapy<br>* XELOX: Oxaliplatin 130mg/m2,iv.,d1;Capecitabine 1000mg/m2,po.,Bid,d1-14; Repeat every 21 days for 3 courses.<br>* Other names: NACT;Procedure: Laparoscopic gastrectomy<br>* Laparoscopic distal gastrectomy with D2 lymph node dissection<br>* Other names: LDG;Drug: Adjuvant Chemotherapy<br>* XELOX: Oxaliplatin 130mg/m2,iv.,d1;Capecitabine 1000mg/m2,po.,Bid,d1-14; Repeat every 21 days for 5 courses.<br>* Other names: ACT;|
| Active Comparator: Open gastrectomy<br>Open distal gastrectomy and D2 lymph node dissection are performed for locally advanced gastric cancer after neoadjuvant chemotherapy. | Drug: Neoadjuvant Chemotherapy<br>* XELOX: Oxaliplatin 130mg/m2,iv.,d1;Capecitabine 1000mg/m2,po.,Bid,d1-14; Repeat every 21 days for 3 courses.<br>* Other names: NACT;Procedure: Open gastrectomy<br>* Open distal gastrectomy with D2 lymph node dissection<br>* Other names: ODG;Drug: Adjuvant Chemotherapy<br>* XELOX: Oxaliplatin 130mg/m2,iv.,d1;Capecitabine 1000mg/m2,po.,Bid,d1-14; Repeat every 21 days for 5 courses.<br>* Other names: ACT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year progression-free survival | In terms of locally advanced gastric cancer, to evaluate the disease free survival rate in laparoscopic subtotal gastrectomy with D2 lymph node dissection at postoperative 3 years compared with open subtotal gastrectomy with D2 lymph node dissection | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | In terms of locally advanced gastric cancer, to evaluate the overall survival rate in laparoscopic subtotal gastrectomy with D2 lymph node dissection at postoperative 3 years compared with open subtotal gastrectomy with D2 lymph node dissection | 36 months | 
| Surgical morbidity | Surgical morbidity is defined as the events which occurs with-in postoperative 30 days, extension of hospitalization and re-hospitalization. It is necessary to evaluate the complication and if it occurs during the hospitalization, it is required to record complication name, date of on-set (postoperatively), grade on Clavien-Dindo Classification and treatment for complication. | 30 days | 
| Surgical mortality | It is defined as the death within postoperative 30 days regardless of postoperative reason. If the patient is transferred to other medication institutes with impossible condition for recovery before death, it is regarded as death. | 30 days | 
| Postoperative recovery index | Postoperatively, the investigator evaluates the patient's recovery condition once a day. Evaluation items for patient's recovery condition: the pain score, the leaving bed time, postoperative gastrointestinal function recovery time and hospital stay. | 2 weeks | 
| Postoperative quality of life | In pre-therapy <7 days, pre-operative <7 days, and post-operative at 12 months after surgery, both the European Organisation for Research and Treatment of Cancer (EORTC) C30 and STO22 are analyzed with quality of life by following methods. In case of EORTC-C30, the analysis is undergone by classifying into 5 functional scales (physical, role, emotional, cognitive, and social functioning), 3 symptom scales (fatigue, pain and nausea, and vomiting), 1 global health status and 6 single items. | Up to 1 year post-operative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally advanced gastric cancer, Laparoscopic distal D2 gastrectomy, Neoadjuvant chemotherapy