Trial for Application of Laparoscopic Total Gastrectomy With Lymph Node Dissection for Gastric Cancer (KLASS-06)

Study Overview
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Brief Summary
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Although Laparoscopic gastrectomy for both early and locally advanced gastric cancer has gained popularity, the use of laparoscopic total gastrectomy for proximal advanced gastric cancer is still limited to some experienced surgeons, because of its technical difficulties in D2 lymph node dissection and anastomoses. Some retrospective and cohort studies regarding laparoscopic total gastrectomy with lymph node dissection suggested the likelihood of application of laparoscopic surgery for proximal gastric cancer. However, there has been no randomized clinical trial comparing results of laparoscopic total gastrectomy with D2 lymph node dissection with open conventional surgery. Therefore, we aimed to verify the efficacy of laparoscopic total gastrectomy with D2(D2-10) lymph node dissection, technical and oncologic safety compared with open surgery via multicenter randomized clinical trial.

Official Title
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Multicenter Randomized Controlled Trial for Application of Laparoscopic Total Gastrectomy With Lymph Node Dissection for Gastric Cancer (KLASS-06)

Conditions
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Gastric Cancer

Intervention / Treatment
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* Procedure: Radical total gastrectomy with D2 (D2 - #10) lymph node dissection by laparoscopic approach
* Procedure: Radical total gastrectomy with D2 (D2 - #10) lymph node dissection by open conventional approach


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are over 20 and below 80 years old Patients who have performance status of ECOG 0 or 1 Patients with American Society of Anesthesiology score of class I to III Patients who are diagnosed with gastric adenocarcinoma not involving Z-line by endoscopy with biopsy Patients with tumors which can be curatively resected by total gastrectomy with lymph node dissection based on preoperative study Patients who have primary gastric carcinoma invaded into over muscle propria, and not into adjacent organ in preoperative studies (cT2   cT4a) Patients who have no metastasis to lymph nodes or limited metastasis to perigastric lymph node metastasis in preoperative studies (cN0   cN2) Patients who agree with participating in the clinical study with informed consents Patients who can be followed for at least 3 years after study enrollment Exclusion Criteria: Patients who have possibility of distant metastasis in preoperative studies Patients who have history of gastric resection with any cause Patients who have complications (bleeding or obstruction) of gastric cancer Patients who are treated by chemo(radio)therapy or endoscopic submucosal dissection for gastric cancer Patients who are diagnosed and treated with other malignancies within 5 years Vulnerable patients Patients who participating or participated in other clinical trial within 6 months

Ages Eligible for Study
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Minimum Age: 20 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
Interventional Model Description: 2-arm randomized controlled study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Laparoscopic group<br>Arm Description: Laparoscopic radical total gastrectomy with D2 (or D2-#10) lymph node dissection | Procedure: Radical total gastrectomy with D2 (D2 - #10) lymph node dissection by laparoscopic approach<br>* Total gastrectomy with D2(D2-10) lymph node dissection by laparoscopic approach The number of trocars is 6 or less Roux-en-Y esophagojejunostomy with any stapling method Enough(negative) margin from tumor LN station #1, 2, 3, 4d, 4sb, 5, 6, 7, 8a, 9, (10), 11p, 11d, 12a should be examined Washing cytology Frozen biopsy for surgical margin at surgeons discretion Complete omentectomy for grossly serosa-involved tumor Combined organ resection only in cholecystectomy and splenectomy Indwelling nasogastric tube and drainage catheter at surgeons discretion D2 lymphadenectomy should be performed : dissection of LN stations No.4d, 4sb, 4sa, 2, 10 (splenic hilar LN can be left according to the clinical stage), 6, 5, 12a, 8a, 9, 7, 1, 3, 11p, 11d with prevention of pancreatic injury during suprapancreatic dissection<br>|
| Active Comparator: Open group<br>Open radical total gastrectomy with D2 (or D2-#10) lymph node dissection | Procedure: Radical total gastrectomy with D2 (D2 - #10) lymph node dissection by open conventional approach<br>* Total gastrectomy with D2(D2-10) lymph node dissection by open conventional approach Roux-en-Y esophagojejunostomy with any stapling method Enough(negative) margin from tumor LN station #1, 2, 3, 4d, 4sb, 5, 6, 7, 8a, 9, (10), 11p, 11d, 12a should be examined Washing cytology Frozen biopsy for surgical margin at surgeons discretion Complete omentectomy for grossly serosa-involved tumor Indwelling nasogastric tube and drainage catheter at surgeons discretion D2 lymphadenectomy should be performed : dissection of LN stations No.4d, 4sb, 4sa, 2, 10 (splenic hilar LN can be left according to the clinical stage), 6, 5, 12a, 8a, 9, 7, 1, 3, 11p, 11d with prevention of pancreatic injury during suprapancreatic dissection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 year relapse-free survival | Non-inferiority of 3 year relapse-free survival rate after laparoscopic radical total gastrectomy and lymphadenectomy for locally advanced gastric cancer comparing with open conventional surgery. The event of relapse-free survival is defined as recurrence after 4 weeks of operation. The censoring is defined as non-traceable patient who cannot be confirmed with recurrence or patient who are alive without recurrence until follow-up. The relapse-free survival time is defined as the time from surgery to event or censoring. | 3 years after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 year overall survival rate |  | 3 years after surgery | 
| 5 year relapse-free and overall survival |  | 5 years after surgery | 
| Morbidity (early period) |  | from Operation day until POD 21 | 
| Morbidity (late period) |  | from POD (Post-Operative Day) 22 until 5 years after surgery | 
| Mortality | death with any cause | at POD 30 | 
| Mortality | death with any cause | at POD 90 | 
| Quality of life(EORTC QLQ-C30) | Quality of life measured by EORTC QLQ-C30(Version 3) The questionnaire was designed to measure cancer patients' physical, psychological and social functions. The questionnaire is composed of 5 multiitem scales (physical, role, social, emotional and cognitive functioning) and 9 single items (pain, fatigue, financial impact, appetite loss, nausea/vomiting, diarrhea, constipation, sleep disturbance and quality of life). | at POD 21 | 
| Quality of life(EORTC QLC STO22) | Quality of life measured by EORTC QLC STO22. The EORTC QLQ-STO 22 module contains 22 items in a similar layout and response format to the EORTC QLQ-C30. The hypothesised scale structure of the module consists of five scales (dysphagia, eating restrictions, pain, reflux and anxiety) and three single items (dry mouth, body image and hair loss). | at POD 21 | 
| Quality of life(EORTC QLQ-C30) | Quality of life measured by EORTC QLQ-C30(Version 3) | 3 months after surgery | 
| Quality of life(EORTC QLC STO22) | Quality of life measured by EORTC QLC STO22. The EORTC QLQ-STO 22 module contains 22 items in a similar layout and response format to the EORTC QLQ-C30. The hypothesised scale structure of the module consists of five scales (dysphagia, eating restrictions, pain, reflux and anxiety) and three single items (dry mouth, body image and hair loss). | 3 months after surgery | 
| Quality of life(EORTC QLQ-C30) | Quality of life measured by EORTC QLQ-C30(Version 3) | 12 months after surgery | 
| Quality of life(EORTC QLC STO22) | Quality of life measured by EORTC QLC STO22. The EORTC QLQ-STO 22 module contains 22 items in a similar layout and response format to the EORTC QLQ-C30. The hypothesised scale structure of the module consists of five scales (dysphagia, eating restrictions, pain, reflux and anxiety) and three single items (dry mouth, body image and hair loss). | 12 months after surgery |