A Clinical Trial of D1+ Versus D2 Distal Gastrectomy for Stage IB & II Advanced Gastric Cancer

Study Overview
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Brief Summary
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In oncological aspect, D1+ lymph node dissection would be enough for early stage gastric cancer in advanced gastric cancer (stage IB/IIA/IIB ).

Detailed Description
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■ Background of Hypothesis A. JCOG (Japanese Clinical Oncology Group) 9501 Study : Addition of aorta lymph node dissection to D2 lymph node dissection does not increase survival rate. Wide range of operation is not always the best treatment. If invasion rate can be kept as minimal as possible while maintaining survival rate, it can lead to more secure operation while also reducing the frequency of complication after the surgery. 20 It may be advantageous for patients in terms of operation time, cost, and quality of life. B. COACT 1001 study A previous study which compared the feasibility of lymph node dissection in open surgery and lapraroscopic surgery for advanced gastric cancer. 11p, 12a lymph node (D2) resection rate: 79.2% and 88.8% respectively in all advance gastric cancer. 11p, 12a lymph node (D2) metastasis rate: 1.9% and 2.9% respectively. Subgroup analysis 11p, 12a lymph node resection in cStage IB/IIA: 74.5-80.0% and 86.7-96.1% respectively. : 0% metastasis rate for both. lymph node dissection in cStage IIB/IIIA: 81.1-82.3% and 87.5-89.2% respectively.: metastasis rates are 2.1% and 2.4-12.1% respectively. Application: 11p and 12a lymph nodes, which belong in D2 lymph nodes, need to be resected in advance gastric cancer in IIB stage or higher. However, in earlier stages of advance gastric cancer, the probability of metastasis is very low; therefore, resection of D1+ lymph nodes, excluding 11p and 12a, is enough.

Official Title
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A Multicenter Randomized Clinical Trial of D1+ Versus D2 Distal Gastrectomy for Stage IB & II Advanced Gastric Cancer

Conditions
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Gastric Adenocarcinoma

Intervention / Treatment
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* Procedure: D2 distal subtotal gastrectomy
* Procedure: D1+ distal subtotal gastrectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : Histologically proven primary gastric adenocarcinoma T1N1, T2N0, T2N1, T3N0, T3N1 by CT scan (AJCC 7th classification) and intraoperative surgical staging prior to resectional procedure Location of primary tumor; antrum, or angle, lower body or mid body of the stomach No evidence of other distant metastasis Aged ≥ 20 year old Performance status (PS) of 0 or 1 on Eastern Cooperative Oncology Group (ECOG) scale No prior treatment of chemotherapy or radiation therapy against any other malignancies, and no prior treatment for gastric cancer including endoscopic mucosal resection Adequate organ functions defined as indicated below: WBC 3000/mm3 - 12,000/mm3 >serum Hemoglobin 8.0 g/dl > serum Platelet 100 000/mm3 < serum AST 100 IU/l <serum ALT 100 IU/l < Total Bilirubin 2.0 mg/dl Written signed informed consent Exclusion Criteria : Active double cancer (synchronous double cancer and metachronous double cancer within five disease-free years), excluding carcinoma in situ (lesions equal to intraepithelial or intramucosal cancer) Gastric remnant cancer ≥T4a in surgical staging before resection N2 or more (number of metastatic lymph nodes ≥3) in CT scan Histologically rare variants in WHO Classification such as Adenosquamous, Hepatoid, Squamous cell, Undifferentiated, , neuroendocrine carcinoma and others Pregnant or breast-feeding women Mental disorder(diagnosed with mental disorder on medical record) systemic administration of corticosteroids(include Herbal Medication) unstable angina or myocardial infarction within 6 months of the trial unstable hypertension severe respiratory disease requiring continuous oxygen therapy previous upper abdominal surgery except laparoscopic cholecystectomy

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| Active Comparator: D2 distal subtotal gastrectomy<br>D2 distal subtotal gastrectomy D2 includes Nos.1.3,4sb,4d,5,6,7,8a,9,11p,and 12a nodes in Japanese classification. Systemic en bloc lymph node dissection is mandatory. Resection margin should be negative for malignancy with intraoperative frozen biopsy | Procedure: D2 distal subtotal gastrectomy<br>* D2 includes Nos.1.3,4sb,4d,5,6,7,8a,9,11p,and 12a nodes in Japanese classification. Systemic en bloc lymph node dissection is mandatory. Resection margin should be negative for malignancy with intraoperative frozen biopsy.<br>|
| Experimental: D1+ distal subtotal gastrectomy<br>D1+ distal subtotal gastrectomy D1+ includes Nos.1,3,4sb,4d,5,6,7,8a,and 9 nodes in Japanese classification. Systemic en bloc lymph node dissection is mandatory. Resection margin should be negative for malignancy with intraoperative frozen biopsy | Procedure: D1+ distal subtotal gastrectomy<br>* D1+ includes Nos.1,3,4sb,4d,5,6,7,8a,and 9 nodes in Japanese classification. Systemic en bloc lymph node dissection is mandatory. Resection margin should be negative for malignancy with intraoperative frozen biopsy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | To test non-inferiority of survival of D1+ gastrectomy versus D2 gastrectomy for clinical stage I B & II advanced gastric cancer | 5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease free survival | 3 year disease free survival | 3 year | 
| Subgroup analysis of Laparoscopic surgery versus open surgery | Subgroup analysis of Laparoscopic surgery versus open surgery in terms of 3 year relapse free survival and 5 year overall survival | 3 year , 5 year | 
| Operating time | Operating time | op day | 
| Early postoperative complications | Early postoperative complications | within 30 days | 
| Long term postoperative complications | Long term postoperative complications | after 30 days | 
| Quality of life of the patients in terms of European quality of life questionnaire (EQ-5D) | Quality of life of the patients in terms of European quality of life questionnaire (EQ-5D) | baseline, 1 week, 1month, 6 month, 1 year, 3 year | 
| Overall cost for the treatment | Overall cost for the treatment (from operative day to discharge day) | operation day to discharge | 
| Finding biomarkers predicting lymph node metastasis and recurrence | Finding biomarkers predicting lymph node metastasis and recurrence for prediction of lymph node metastasis and recurrence | 3 year |