Multicenter Study on Laparoscopic Total Gastrectomy for Advanced Gastric Cancer

Official title

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

Overview

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

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.

Interventions

• Procedure Laparoscopic total gastrectomy
  LTG with D2 lymphadenectomy for patients with locally advanced gastric cancer (clinical stage T2-4aN0-3M0)
• Procedure Open total gastrectomy
  OTG with D2 lymphadenectomy for patients with locally advanced gastric cancer (clinical stage T2-4aN0-3M0)

Primary outcome measures

• Overall survival [Time frame: 3 years]

Secondary outcome measures (6)

• 3-year overall survival rate [Time frame: 3 years]
• 3-year disease free survival rate [Time frame: 3 years]
• Early morbidity rate [Time frame: 30 days]
• Early mortality rate [Time frame: 30 days]
• 3-year recurrence pattern [Time frame: 3 years]
• Postoperative recovery course [Time frame: 30 days]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• ZhongShan hospital FuDan university — Shanghai

Publications

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. PMID 30207593
• Yang L, Zheng R, Wang N, Yuan Y, Liu S, Li H, Zhang S, Zeng H, Chen W. Incidence and mortality of stomach cancer in China, 2014. Chin J Cancer Res. 2018 Jun;30(3):291-298. doi: 10.21147/j.issn.1000-9604.2018.03.01. PMID 30046223
• Yamashita H, Seto Y, Sano T, Makuuchi H, Ando N, Sasako M; Japanese Gastric Cancer Association and the Japan Esophageal Society. Results of a nation-wide retrospective study of lymphadenectomy for esophagogastric junction carcinoma. Gastric Cancer. 2017 Mar;20(Suppl 1):69-83. doi: 10.1007/s10120-016-0663-8. Epub 2016 Oct 28. PMID 27796514
• Liu K, Yang K, Zhang W, Chen X, Chen X, Zhang B, Chen Z, Chen J, Zhao Y, Zhou Z, Chen L, Hu J. Changes of Esophagogastric Junctional Adenocarcinoma and Gastroesophageal Reflux Disease Among Surgical Patients During 1988-2012: A Single-institution, High-volume Experience in China. Ann Surg. 2016 Jan;263(1):88-95. doi: 10.1097/SLA.0000000000001148. PMID 25647058
• Kitano S, Iso Y, Moriyama M, Sugimachi K. Laparoscopy-assisted Billroth I gastrectomy. Surg Laparosc Endosc. 1994 Apr;4(2):146-8. PMID 8180768
• Kim W, Kim HH, Han SU, Kim MC, Hyung WJ, Ryu SW, Cho GS, Kim CY, Yang HK, Park DJ, Song KY, Lee SI, Ryu SY, Lee JH, Lee HJ; Korean Laparo-endoscopic Gastrointestinal Surgery Study (KLASS) Group. Decreased Morbidity of Laparoscopic Distal Gastrectomy Compared With Open Distal Gastrectomy for Stage I Gastric Cancer: Short-term Outcomes From a Multicenter Randomized Controlled Trial (KLASS-01). Ann S PMID 26352529
• Katai H, Mizusawa J, Katayama H, Takagi M, Yoshikawa T, Fukagawa T, Terashima M, Misawa K, Teshima S, Koeda K, Nunobe S, Fukushima N, Yasuda T, Asao Y, Fujiwara Y, Sasako M. Short-term surgical outcomes from a phase III study of laparoscopy-assisted versus open distal gastrectomy with nodal dissection for clinical stage IA/IB gastric cancer: Japan Clinical Oncology Group Study JCOG0912. Gastric Ca PMID 27718137
• Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer. 2021 Jan;24(1):1-21. doi: 10.1007/s10120-020-01042-y. Epub 2020 Feb 14. No abstract available. PMID 32060757

Identifiers

NCT: NCT04710758 · ZSGC-006

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗