Multicenter Study on Laparoscopic Total Gastrectomy for Advanced Gastric Cancer

Study Overview
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Brief Summary
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CLASS-07 trial is a prospective, multicenter, randomized controlled trial for comparison of long-term outcomes between laparoscopic total gastrectomy (LTG) and open total gastrectomy (OTG) in patients with locally advanced gastric cancer (clinical stage T2-4aN0-3M0). The primary purpose of this study is to evaluate the overall survival and determine the efficacy of LTG compared with OTG for locally advanced gastric cancer. The second purpose is to evaluate the 3-year overall survival rate, 3-year disease free survival rate, morbidity and mortality rates, 3-year recurrence pattern and postoperative recovery course of the patients enrolled in this study.

Detailed Description
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Gastric cancer is a significant global health problem, especially in East Asia. With an increase in the incidences of proximal gastric cancer over the last decades, the value of total gastrectomy is more emphasized. Laparoscopic total gastrectomy (LTG) has become an attracting option for surgeons due to its well-known advantages. However, more evidence is needed to support the safety and efficacy of LTG in locally advanced gastric cancer. Recently，a multicenter, open-label, noninferiority, randomized clinical trial (CLASS-02) launched by Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group compared the safety of LTG for clinical stage I gastric cancer with open total gastrectomy (OTG). The overall morbidity and mortality rates were 19.1% in the LTG group and 20.2% in the OTG group, which was not significantly different (rate difference, -1.1%). This study demonstrated that LTG can be safely performed by experienced surgeons for clinical stage I gastric cancer. However, there hasn't been any prospective randomized clinical trial study evaluating the safety and efficacy of LTG in advanced gastric cancer. This CLASS-07 trial is a prospective, multicenter, randomized controlled trial for comparison of long-term outcomes between LTG and OTG in patients with locally advanced gastric cancer (clinical stage T2-4aN0-3M0). The primary purpose of this study is to evaluate the overall survival and determine the efficacy of LTG compared with OTG for locally advanced gastric cancer. The second purpose is to evaluate the 3-year overall survival rate, 3-year disease free survival rate, morbidity and mortality rates, 3-year recurrence pattern and postoperative recovery course of the patients enrolled in this study.

Official Title
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Prospective Randomized Controlled Multicenter Clinical Trial For Comparison Of Long-term Outcomes Between Laparoscopic And Open Total Gastrectomy In Patients With Locally Advanced Gastric Cancer

Conditions
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Stomach Neoplasms

Intervention / Treatment
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* Procedure: Laparoscopic total gastrectomy
* Procedure: Open total gastrectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-75 years Tumor located in the middle or upper third of the stomach, and curative resection is expected to be achievable by total gastrectomy with D2 lymphadenectomy (also apply to multiple primary cancers); Primary lesion is pathologically diagnosed as gastric adenocarcinoma, such as papillary adenocarcinoma, tubular adenocarcinoma, mucinous adenocarcinoma, poorly cohesive carcinoma (including signet ring cell carcinoma and other variants), and mixed adenocarcinoma; Clinical stage T2-4aN0-3M0 (According to AJCC-8th TNM staging system); Expected survival > 6 months No invasion to Z-line; BMI (Body Mass Index) < 30 kg/m2 No history of upper abdominal surgery (except for laparoscopic cholecystectomy); No prior treatment of chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc Preoperative performance status (ECOG，Eastern Cooperative Oncology Group) of 0 or 1 Preoperative ASA (American Society of Anesthesiologists) scoring: I-III Sufficient organ functions Written informed consent Exclusion Criteria: Preoperative examinations indicate regional fusion of enlarged lymph nodes (max diameter ≥ 3.0cm) or enlargment of spleen hilus lymph nodes Women during pregnancy or breast-feeding Synchronous or metachronous (within 5 years) malignancies Body temperature ≥ 38℃ before surgery or infectious disease with a systemic therapy indicated Severe mental disease Severe respiratory disease, FEV1 < 50% of predicted Severe hepatic and renal dysfunction Unstable angina pectoris or history of myocardial infarction within 6 months History of cerebral infarction or cerebral hemorrhage within 6 months Continuous systemic steroid therapy within 1 month (except for topical use) Gastric cancer complications (bleeding, perforation, obstruction) that requiring emergency surgery Patients are participating or have participated in another clinical trial (within 6 months)

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: Laparoscopic total gastrectomy<br>The surgeon will perform LTG with D2 lymphadenectomy for patients enrolled in this group. | Procedure: Laparoscopic total gastrectomy<br>* LTG with D2 lymphadenectomy for patients with locally advanced gastric cancer (clinical stage T2-4aN0-3M0)<br>* Other names: Experimental group (LTG);|
| Active Comparator: Open total gastrectomy<br>The surgeon will perform OTG with D2 lymphadenectomy for patients enrolled in this group. | Procedure: Open total gastrectomy<br>* OTG with D2 lymphadenectomy for patients with locally advanced gastric cancer (clinical stage T2-4aN0-3M0)<br>* Other names: Control group (OTG);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival (OS) was defined as the time from randomization to death from any cause | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year overall survival rate | # of patients who are still alive at 3 years out of all study patients | 3 years | 
| 3-year disease free survival rate | # of patients who are free of gastric cancer at 3 years out of all study patients | 3 years | 
| Early morbidity rate | The early morbidity are defined as the event observed within 30 days following surgery, including intraoperative and postoperative complications | 30 days | 
| Early mortality rate | The early mortality are defined as the event observed within 30 days following surgery, including intraoperative and postoperative death | 30 days | 
| 3-year recurrence pattern | Recurrence patterns are classified into five categories at the time of first diagnosis: locoregional, hematogenous, peritoneal, distant lymph node, and mixed type | 3 years | 
| Postoperative recovery course | Time to first ambulation, flatus, liquid diet, and soft diet are used to assess the postoperative recovery course, which is a composite outcome measure. | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stomach Neoplasms, Laparoscopic total gastrectomy, Open total gastrectomy