Laparoscopic D2 Distal Gastrectomy Following Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancers

Study Overview
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Brief Summary
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Gastric cancer is the third major cancer of global cancer-related death. In China, the early diagnosis rate of gastric cancer is relatively low, and most patients are with locally advanced tumor stage. The neoadjuvant chemotherapy (NAC) can bring the survival advantage for gastric cancer patients with locally advanced tumor stage. The primary goal of NAC is to control the micrometastasis and/or progression of the primary lesion in order to improve potential of radical gastrectomy. NAC is recommended for patients with locally advanced stage (T2-4Nx) according to the latest NCCN Gastric Cancer Guidelines. Laparoscopy distal gastrectomy (LDG) can achieve a better postoperative short-term recovery than the traditional open distal gastrectomy (ODG), which can reduce the intraoperative blood loss and to shorten the postoperative hospital stay. Therefore, Enhanced Recovery After Surgery program of gastric cancer surgery recommends the use of minimally invasive surgery. For long-term survival outcomes, there is limited evidence supported that laparoscopic gastrectomy is comparable open gastrectomy. Therefore, due to the lack of high-quality prospective clinical trial results, whether advanced tumor is suitable for laparoscopic surgery is still controversial. Therefore, some multi-center prospective randomized controlled trials have been carried out, compared safety and long-term survival outcome between laparoscopic and open gastrectomy in locally advanced gastric cancer patients. CLASS-01 trials reported that for locally advanced gastric cancers, laparoscopic D2 distal gastrectomy is safe and feasible. Patient's surgical tolerance and stress response may be inhibited after the treatment of NAC. The aim of this trial is to confirm the safety of laparoscopy distal D2 radical gastrectomy for the treatment of after neoadjuvant chemotherapy gastric cancer patients (cT3-4a, N+, M0) in terms of postoperative complications.

Detailed Description
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This is a prospective, multi-centers, open-label, single-arm study, and the aim of this trial is to evaluate the safety of laparoscopic distal D2 radical gastrectomy for the treatment of locally advanced gastric cancer (cT3-4a, N-/+, M0) after neoadjuvant chemotherapy.

Official Title
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Laparoscopic D2 Distal Gastrectomy Following Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancers: A Prospective Multicenter Trial

Conditions
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Complications, Postoperative, Surgery--Complications, Cancer of Stomach, Chemotherapy Effect

Intervention / Treatment
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* Procedure: Laparoscopic D2 distal gastrectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First Round Inclusion Criteria Age from over 18 to under 75 years; Primary gastric adenocarcinoma (including pap, tub, muc, sig, and por) confirmed pathologically by endoscopic biopsy; cT3-4a, N-/+, M0 according to the AJCC 8th Cancer Staging Manual; Without peritoneal metastasis (examined by laparoscopic examination); Radical resection (R0) through distal subtotal gastrectomy with D2 lymphadenectomy is anticipated; Performance status 0 or 1 (Eastern Cooperative Oncology Group) ; ASA (American Society of Anesthesiology) score ≤ 3; Normal hemodynamic indices: Blood cell count: HB ≥ 90g/L, ANC ≥ 1.5×109/L, PLT ≥ 80×109/L; Liver and renal function: BIL<1.5 times of the upper limit of normal reference values, ALT and AST<2.5 times of the upper limit of normal reference values, and Crea≤1 time of upper limits of normal reference values. Second Round Inclusion Criteria Therapeutic response rating after neoadjuvant chemotherapy is CR, PR, SD, or Therapeutic response rating after neoadjuvant chemotherapy is PD, tumor is expected to have radical resection; Subjects are still willing to continue participating in this clinical trial. Exclusion Criteria: First Round Exclusion Criteria History of upper abdominal surgery (include endoscopic mucosal resection or endoscopic submucosal dissection, except for laparoscopic cholecystectomy); History of acute pancreatitis; Enlarged or bulky regional lymph node (diameter>3cm) by imaging exam; Patients have received neoadjuvant therapy prior to screen work; History of other malignant disease within the past five years; History of cerebrovascular accident within the past six months; History of continuous systematic administration of corticosteroids within the past month; Scheduled simultaneous surgery for other disease; Emergency surgery due to complication (bleeding, obstruction or perforation) caused by gastric cancer; Pyloric obstruction; FEV1<50% of predicted value; Women who are pregnant or lactating at the time of screening; Severe mental disorder; Participating in other clinical studies; Refused to sign the informed consent; Second Round Exclusion Criteria Therapeutic response rating after neoadjuvant chemotherapy is PD, involvement of adjacent structures(T4b), distal metastasis(M1), or enlarged or bulky regional lymph node (diameter>3cm) by preoperative imaging Patients cannot complete 3 cycles of chemotherapy due to intolerance; After 3 cycles of neoadjuvant chemotherapy, patients cannot tolerate surgery due to severe adverse reactions, or ASA score ≥ 4 ; Patients undertake emergency operation due to tumor bleeding, perforation or obstruction during chemotherapy; After signing the informed consent, the patient withdraws from this clinical trial. Withdrawal Criteria After Second Round: Intro-abdominal metastasis of primary cancer is revealed intraoperatively; Primary cancer is confirmed to be un-resectable intraoperatively.

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
Intervention Model: Single Group Assignment
Interventional Model Description: Laparoscopic D2 distal gastrectomy after 3-Cycle XELOX neo-adjuvant chemotherapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Laparoscopic D2 distal gastrectomy after 3-Cycle XELOX neo-adjuvant chemotherapy | Procedure: Laparoscopic D2 distal gastrectomy<br>* Laparoscopic D2 distal gastrectomy after 3-Cycle XELOX neo-adjuvant chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative overall morbidity rate | The proportion value will be calculated by the number of patients with any operative complication as the numerator and the number of patients undergoing surgical treatment as the denominator. | Postoperative 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative mortality rate | Mortality will be calculated as the ratio between the number of patients who died as numerator and number of all patients undergoing surgical treatment as the denominator. | Postoperative 30 days | 
| R0 resection rate | Number of patients underwent gastrectomy for the denominator, number of R0 resection patients is numerator, the ratio is the R0 resection rate. The definition of R0 resection is according to the Japanese gastric cancer treatment guidelines 2014 (ver. 4)（Gastric Cancer. 2017 Jan;20(1):1-19.）. | The day of surgery | 
| Completion rate of laparoscopic surgery | Ratio will be calculated with the number of patients complete the laparoscopic gastrectomy as the numerator, and number of all patients undergoing laparoscopic surgical treatment as the denominator. | The day of surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mortality, morbidity, neoadjuvant chemotherapy, laparoscopic gastrectomy, gastric cancer