Efficacy of Laparoscopic Subtotal Gastrectomy With D2 Lymph Node Dissection for Locally Advanced Gastric Cancer (KLASS-02-RCT)

• ClinicalTrials.gov Identifier: NCT01456598
• Recruitment Status: Completed
• First Posted: October 21, 2011
• Last Update Posted: November 29, 2018
• Sponsor: Ajou University School of Medicine
• Information provided by (Responsible Party): Sang-Uk Han, Ajou University School of Medicine

Study Description

Brief Summary:

• It was confirmed that the laparoscopic surgery decreases the postoperative pain and reduces the recovery periods in the various surgical fields such as cholecystectomy and colectomy etc. Also, there are clinical evidences that the laparoscopic surgery is applicable to malignant tumor according to the development of surgical techniques and medical instruments.
• In case of early stage of gastric cancer, as the diverse clinical evidences, the gastrectomy has been commonly applied, however, the opening surgery is still applied for advanced gastric cancer due to lack of clinical evidence.
• In Korea, approximately 38% of patients who undergo surgery for gastric cancer are diagnosed by T2-T3 (AJCC 6th edition) (www.i-kgca.or.kr, National gastric cancer registration business in 2009). There are various clinical evidences to apply laparoscopic surgery to the patients, however, most of them are retrospective or cohort study results.
• For the clinical application of surgical treatment regarding locally advanced gastric cancer using laparoscopic surgical technique, it requires the confirmation of definite execution for laparoscopic gastrectomy and D2 lymph node dissection and the safety of surgery and oncological usefulness should be verified.
• In order for this, it is only possible to confirm through the comparison of short-term surgical results (complications, mortalities, operative time and duration of hospitalization etc) and long-term results (survival rates and recurrence rates etc) between laparoscopic surgery and opening surgery based on the multicenter large-sized randomized prospective study with current standard treatment.

Condition or disease	Intervention/treatment	Phase
Gastric Cancer	Procedure: Laparoscopic gastrectomy; Procedure: Open gastrectomy	Not Applicable

Detailed Description:

Participating Surgeons

• Prior to this clinical trial, only the surgeons who are considered to have the standardization by participating the assignment entitled with "KLASS-02-QC: Standardization of D2 Lymphadenectomy and Surgical Quality Control for KLASS-02 Trial"(ClinicalTrials.gov No: NCT01283893).

Patients Registration

• It is required to ensure that the patients meet the inclusion criteria for this clinical trial, are free from any items of exclusion criteria, are explained about the participation in the clinical trial along with the informed consent forms.
• After rechecking the patients with the registration check list by accessing the web-based randomized program provided from Ajou University clinical trial center.

Randomization

• The registration randomization should be done with 1:1 ratio for each researcher.
• Baseline number (BN) should be provided to the subjects in the order of acquisition of informed consent form. Based on the subjects who are selected as the appropriate subjects in the end, the allocation number (AN) shall be provided in the order of randomized allocation table.

Procedure

• Operations are performed according to the allocated group.

Adjuvant Treatment

• If it is under Stage II and Stage III in the final postoperative pathology, the adjuvant chemotherapy based on 5-FU.

Evaluation of efficacy and safety

• 3-year Relapse free survival rate and overall survival rate of the patients who undergo laparoscopic and open subtotal gastrectomy and D2 lymph node dissection.
• Analysis of recovery after laparoscopic and open subtotal gastrectomy and D2 lymph node dissection.
• Postoperative complications of the patients who undergo laparoscopic and open subtotal gastrectomy and D2 lymph node dissection within postoperative 3 weeks and later.
• The quality of life at preoperative, postoperative 25 days and 1 years using recovery index such as recovery of postoperative intestinal hypermotility, meals and duration of hospitalization, EORTC-C30 and STO22 questionnaire between the patients who underwent laparoscopic and open subtotal gastrectomy and D2 lymph node dissection.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1050 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective Multicenter Randomized Controlled Clinical Trial for Comparison Between Laparoscopic and Open Subtotal Gastrectomy With D2 Lymph Node Dissection for Locally Advanced Gastric Cancer
• Actual Study Start Date: November 21, 2011
• Actual Primary Completion Date: June 2, 2018
• Actual Study Completion Date: June 2, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Laparoscopic gastrectomy; Laparoscopic subtotal gastrectomy and D2 lymph node dissection are performed for locally advanced gastric cancer.	Procedure: Laparoscopic gastrectomy; After laparoscopic observation, the possibility of surgery can be considered by examining inside of abdomen.; The surgeon undergoes laparoscopic subtotal gastrectomy and D2 lymph node dissection; After lymph node dissection, it is possible to undergo gastrectomy on appropriate part and reconstruction under small incision or laparoscopic view.; As the reconstruction, one of the techniques like Billroth I, Billroth II and Roux en Y and so on is applied and there is no limitation on use of appliance.; Other Names: Group A; LDG
Active Comparator: Open gastrectomy; Open subtotal gastrectomy and D2 lymph node dissection are performed for locally advanced gastric cancer.	Procedure: Open gastrectomy; After laparotomy, the possibility of surgery can be considered by examining inside of abdomen.; The surgeon undergoes open subtotal gastrectomy and D2 lymph node dissection; After lymph node dissection, one of the techniques likes Billroth I, Billroth II and Roux en Y and so on is applied and there is no limitation on use of appliance.; Other Names: Group B; ODG

Outcome Measures

Primary Outcome Measures :

1. 3 year relapse free survival [ Time Frame: 36 months ]
   In terms of locally advanced gastric cancer, to examine the non-inferiority of disease free sur-vival rate in laparoscopic subtotal gastrectomy with D2 lymph node dissection at postoperative 3 years compared with open subtotal gastrectomy with D2 lymph node dissection

Secondary Outcome Measures :

1. Early postoperative complication [ Time Frame: 3 weeks ]
   Early postoperative complication is defined as the events which occurs with-in postoperative 21 days, extension of hospitalization and rehospitaliation. It is necessary to evaluate the complication and if it occurs during the hospitalization, it is required to record complication name and date of on-set (postoperatively) and treatment for complication.
2. Postoperative mortality [ Time Frame: 90 days ]
   It is defined as the death within postoperative 90 days regardless of postoperative reason. If the patient is transferred to other medication institutes with impossible condition for revocery be-fore death, it is regarded as death.
3. Late postoperative complication [ Time Frame: 36 months ]
   Late postoperative complication is defined the events which occurs after postoperative 21 days. It is necessary to evaluate the complication. it is required to record complication name and date of on-set (postoperatively) and treatment for complication.
4. Postoperative recovery index [ Time Frame: 4 weeks ]
   Postoperatively, the examiner evaluates the patient's recovery condition (gas exhaust) once a day. Evaluation items for patient's recovery condition: record the meal process once a day and inquire the pain score (10-scored scale) and blood test results during postoperative hospitalization.
5. Postoperative quality of life [ Time Frame: preoperative, 3 weeks, 12 months ]
   On preoperative, postoperative 3 weeks and postoperative 12 months, both 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 fungtioning), 3 symptom scales (fatigue, pain and nausea, and vomiting), 1 global health status and 6 single items.
6. 3 years overall survival [ Time Frame: 6, 12, 18, 24, 30 and 36 months ]
   As one of the secondary endpoints, 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. The schedule of visit is based on every 3 months for 3 years. If subjects cannot visit every 3 months, the investigator can arrange the schedule. However, enrolled should visit every 6 months for 3 years.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• The patient from over 20 years to under 80 years
• The patient with the capability for ECOG (Eastern Cooperative Oncology Group performance status) is ranged between 0 and 1
• The patient included between ASA score (American society of anesthesiology) class I and III
• The patient who is diagnosed as gastric adenocarcinoma under preoperative endoscopic biopsy
• The patient who is diagnosed as locally advanced gastric cancer with the suspicious infiltration of over muscular layer without infiltration on adjacent organs, and without or with lymph node metastasis limited to perigastric or around stomach left gastric artery at the preoperative examination.
• The patient who is suitable for subtotal resection in the preoperative examination
• The patient who is fully explained about purpose of trial and contents prior to the participation into this study and signed on the informed consent approved by Institutional Review Board according to own opinion

Exclusion Criteria:

• The patient who shows distant metastasis under preoperative examination
• The patient with medical history for gastrectomy in the past
• The patient with complication (complete obstruction and perforation) by gastric cancer
• The patient who undergoes anticancer or radiologic therapy prior to the operation or who undergoes endoscopic submucous dissection for currently diagnosed gastric cancer
• The patient who undergoes surgery or anti-cancer radiologic therapy for primary cancer within 5 years
• Vulnerable patients (lack of capacity for decision making, pregnant women (or under planning))
• The patient who has participated into another clinical trial within recent 6 months or who is participating into another trial
• The patient with double cancer of activity and synchronization

Contacts and Locations

Locations

Korea, Republic of

Department of Surgery , SOON CHUN HYANG UNIVESITY HOSPITAL

Bucheon, Korea, Republic of

Keimyung University Dongsan Medical Center

Daegu, Korea, Republic of, 700-712

Copyright National Cancer Center

Goyang-si, Korea, Republic of

Chonnam National University Hwasun Hospital

Hwasun, Korea, Republic of, 519-809

Incheon St, Mary's Hostpial, The Catholic University of Korea

Incheon, Korea, Republic of, 403-720

Dong-A University Hospital

Pusan, Korea, Republic of, 602-715

Department of Surgery, Seoul National University BUNDANG Hospital

Seongnam, Korea, Republic of

Department of Surgery, Seoul National University Hospital

Seoul, Korea, Republic of, 110-799

Yonsei University Severance Hospital

Seoul, Korea, Republic of, 120-752

Yeoeuido St. Mary's Hospital, The Catholic University of Korea

Seoul, Korea, Republic of, 150-713

Department of surgery, GANGNAM SEVERANCE HOSPITAL

Seoul, Korea, Republic of

EWHA Womans university medical center

Seoul, Korea, Republic of

Ajou University Hospital

Suwon, Korea, Republic of, 443-749

Sponsors and Collaborators

Ajou University School of Medicine

Investigators

• Principal Investigator: San-Uk Han, M.D., Ph.D.; Department of Surgery, Ajou University School of Medicine

More Information

Additional Information:

Institutional Review Board, Ajou University Hospital 

Ajou University Hospital 

The Korean Gastric Cancer Association 

Publications:

Kitano S, Iso Y, Moriyama M, Sugimachi K. Laparoscopy-assisted Billroth I gastrectomy. Surg Laparosc Endosc. 1994 Apr;4(2):146-8. Erratum In: Surg Laparosc Endosc. 2013 Oct;23(5):480.

Kim W, Song KY, Lee HJ, Han SU, Hyung WJ, Cho GS. The impact of comorbidity on surgical outcomes in laparoscopy-assisted distal gastrectomy: a retrospective analysis of multicenter results. Ann Surg. 2008 Nov;248(5):793-9. doi: 10.1097/SLA.0b013e3181887516.

Kim HH, Hyung WJ, Cho GS, Kim MC, Han SU, Kim W, Ryu SW, Lee HJ, Song KY. Morbidity and mortality of laparoscopic gastrectomy versus open gastrectomy for gastric cancer: an interim report--a phase III multicenter, prospective, randomized Trial (KLASS Trial). Ann Surg. 2010 Mar;251(3):417-20. doi: 10.1097/SLA.0b013e3181cc8f6b.

Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. doi: 10.1056/NEJMoa072252. Erratum In: N Engl J Med. 2008 May 1;358(18):1977.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Son SY, Hur H, Hyung WJ, Park YK, Lee HJ, An JY, Kim W, Kim HI, Kim HH, Ryu SW, Kim MC, Kong SH, Cho GS, Kim JJ, Park DJ, Ryu KW, Kim YW, Kim JW, Lee JH, Yang HK, Han SU; Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS) Group. Laparoscopic vs Open Distal Gastrectomy for Locally Advanced Gastric Cancer: 5-Year Outcomes of the KLASS-02 Randomized Clinical Trial. JAMA Surg. 2022 Oct 1;157(10):879-886. doi: 10.1001/jamasurg.2022.2749.

Hyung WJ, Yang HK, Park YK, Lee HJ, An JY, Kim W, Kim HI, Kim HH, Ryu SW, Hur H, Kim MC, Kong SH, Cho GS, Kim JJ, Park DJ, Ryu KW, Kim YW, Kim JW, Lee JH, Han SU; Korean Laparoendoscopic Gastrointestinal Surgery Study Group. Long-Term Outcomes of Laparoscopic Distal Gastrectomy for Locally Advanced Gastric Cancer: The KLASS-02-RCT Randomized Clinical Trial. J Clin Oncol. 2020 Oct 1;38(28):3304-3313. doi: 10.1200/JCO.20.01210. Epub 2020 Aug 20.

• Responsible Party: Sang-Uk Han, Professor, Department of Surgery, Ajou University School of Medicine, Ajou University School of Medicine
• ClinicalTrials.gov Identifier: NCT01456598
• Other Study ID Numbers: AJIRB-MED-MDB-11-233
• First Posted: October 21, 2011
• Last Update Posted: November 29, 2018
• Last Verified: November 2018

Keywords provided by Sang-Uk Han, Ajou University School of Medicine:

Stomach neoplasm; Laparoscopy

Additional relevant MeSH terms:

Stomach Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases