Laparoscopic D2 Distal Gastrectomy Following Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancers (CLASS-03a)

Laparoscopic D2 Distal Gastrectomy Following Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancers: A Prospective Multicenter Trial

Gastric cancer is the third major cancer of global cancer-related death. In China, the early diagnosis rate of gastric cancer is relatively low, and most patients are with locally advanced tumor stage. The neoadjuvant chemotherapy (NAC) can bring the survival advantage for gastric cancer patients with locally advanced tumor stage. The primary goal of NAC is to control the micrometastasis and/or progression of the primary lesion in order to improve potential of radical gastrectomy. NAC is recommended for patients with locally advanced stage (T2-4Nx) according to the latest NCCN Gastric Cancer Guidelines.

Laparoscopy distal gastrectomy (LDG) can achieve a better postoperative short-term recovery than the traditional open distal gastrectomy (ODG), which can reduce the intraoperative blood loss and to shorten the postoperative hospital stay. Therefore, Enhanced Recovery After Surgery program of gastric cancer surgery recommends the use of minimally invasive surgery. For long-term survival outcomes, there is limited evidence supported that laparoscopic gastrectomy is comparable open gastrectomy. Therefore, due to the lack of high-quality prospective clinical trial results, whether advanced tumor is suitable for laparoscopic surgery is still controversial. Therefore, some multi-center prospective randomized controlled trials have been carried out, compared safety and long-term survival outcome between laparoscopic and open gastrectomy in locally advanced gastric cancer patients. CLASS-01 trials reported that for locally advanced gastric cancers, laparoscopic D2 distal gastrectomy is safe and feasible.

Patient's surgical tolerance and stress response may be inhibited after the treatment of NAC. The aim of this trial is to confirm the safety of laparoscopy distal D2 radical gastrectomy for the treatment of after neoadjuvant chemotherapy gastric cancer patients (cT3-4a, N+, M0) in terms of postoperative complications.

Study Overview

• Status: Recruiting
• Conditions: Surgery--Complications; Chemotherapy Effect; Cancer of Stomach; Complications, Postoperative
• Intervention / Treatment: Procedure: Laparoscopic D2 distal gastrectomy

Detailed Description

This is a prospective, multi-centers, open-label, single-arm study, and the aim of this trial is to evaluate the safety of laparoscopic distal D2 radical gastrectomy for the treatment of locally advanced gastric cancer (cT3-4a, N-/+, M0) after neoadjuvant chemotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 166
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wei-Han Zhang, M.D. Ph.D.; Phone Number: 02885422480

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Not yet recruiting
      • Chinese PLA General Hospital
    • Beijing, Beijing, China, 10000
      • Not yet recruiting
      • Peking University Cancer Hospital and Institute
  • Chongqing
    • Chongqing, Chongqing, China, 404100
      • Not yet recruiting
      • Southwest Hospital, The Third Military Medical University
      • Contact: Pei-Wu Yu, M.D.,Ph.D.
      • Principal Investigator: Pei-Wu Yu, M.D.,Ph.D.
  • Fujian
    • Fuzhou, Fujian, China
      • Not yet recruiting
      • Fujian Medical University Union Hospital
      • Contact: Chang-Ming Huang
  • Guangdong
    • Guangzhou, Guangdong, China
      • Not yet recruiting
      • Nanfang Hospital
      • Contact: Guo-Xin Li
    • Guangzhou, Guangdong, China, 51000
      • Not yet recruiting
      • Guangdong General Hospital
  • Heilonngjiang
    • Harbin, Heilonngjiang, China
      • Not yet recruiting
      • Harbin Medical University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • The First Affiliated Hospital with Nanjing Medical University
      • Contact: Ze-Kuan Xu
  • Jilin
    • Changchun, Jilin, China
      • Not yet recruiting
      • First Hospital of Jilin University
      • Contact: Jian Suo
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Not yet recruiting
      • Zhongshan Hospital, Fudan University
    • Shanghai, Shanghai, China
      • Not yet recruiting
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China
      • Not yet recruiting
      • Renji Hospital, Shanghai Jiaotong University
      • Contact: Gang Zhao
    • Shanghai, Shanghai, China
      • Not yet recruiting
      • Ruijin Hospital, Shanghai Jiaotong University
  • Shanxi
    • Xian, Shanxi, China, 710000
      • Not yet recruiting
      • Tangdu Hospital, Fourth Military Medical University
      • Contact: Xian-Li He, M.D.,Ph.D.
      • Principal Investigator: Xian-Li He, M.D.
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital, Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • Sir Run Run Shaw Hospital, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• First Round Inclusion Criteria

  1. Age from over 18 to under 75 years;
  2. Primary gastric adenocarcinoma (including pap, tub, muc, sig, and por) confirmed pathologically by endoscopic biopsy;
  3. cT3-4a, N-/+, M0 according to the AJCC 8th Cancer Staging Manual;
  4. Without peritoneal metastasis (examined by laparoscopic examination);
  5. Radical resection (R0) through distal subtotal gastrectomy with D2 lymphadenectomy is anticipated;
  6. Performance status 0 or 1 (Eastern Cooperative Oncology Group) ;
  7. ASA (American Society of Anesthesiology) score ≤ 3;
  8. Normal hemodynamic indices:
  1. Blood cell count: HB ≥ 90g/L, ANC ≥ 1.5×109/L, PLT ≥ 80×109/L;
  2. Liver and renal function: BIL<1.5 times of the upper limit of normal reference values, ALT and AST<2.5 times of the upper limit of normal reference values, and Crea≤1 time of upper limits of normal reference values.

• Second Round Inclusion Criteria

  1. Therapeutic response rating after neoadjuvant chemotherapy is CR, PR, SD, or Therapeutic response rating after neoadjuvant chemotherapy is PD, tumor is expected to have radical resection;
  2. Subjects are still willing to continue participating in this clinical trial.

Exclusion Criteria:

• First Round Exclusion Criteria

  1. History of upper abdominal surgery (include endoscopic mucosal resection or endoscopic submucosal dissection, except for laparoscopic cholecystectomy);
  2. History of acute pancreatitis;
  3. Enlarged or bulky regional lymph node (diameter>3cm) by imaging exam;
  4. Patients have received neoadjuvant therapy prior to screen work;
  5. History of other malignant disease within the past five years;
  6. History of cerebrovascular accident within the past six months;
  7. History of continuous systematic administration of corticosteroids within the past month;
  8. Scheduled simultaneous surgery for other disease;
  9. Emergency surgery due to complication (bleeding, obstruction or perforation) caused by gastric cancer;
  10. Pyloric obstruction;
  11. FEV1<50% of predicted value;
  12. Women who are pregnant or lactating at the time of screening;
  13. Severe mental disorder;
  14. Participating in other clinical studies;
  15. Refused to sign the informed consent;

• Second Round Exclusion Criteria

  1. Therapeutic response rating after neoadjuvant chemotherapy is PD, involvement of adjacent structures(T4b), distal metastasis(M1), or enlarged or bulky regional lymph node (diameter>3cm) by preoperative imaging
  2. Patients cannot complete 3 cycles of chemotherapy due to intolerance;
  3. After 3 cycles of neoadjuvant chemotherapy, patients cannot tolerate surgery due to severe adverse reactions, or ASA score ≥ 4 ;
  4. Patients undertake emergency operation due to tumor bleeding, perforation or obstruction during chemotherapy;
  5. After signing the informed consent, the patient withdraws from this clinical trial.

Withdrawal Criteria After Second Round:

1. Intro-abdominal metastasis of primary cancer is revealed intraoperatively;
2. Primary cancer is confirmed to be un-resectable intraoperatively.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental group; Laparoscopic D2 distal gastrectomy after 3-Cycle XELOX neo-adjuvant chemotherapy	Procedure: Laparoscopic D2 distal gastrectomy; Laparoscopic D2 distal gastrectomy after 3-Cycle XELOX neo-adjuvant chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative overall morbidity rate	The proportion value will be calculated by the number of patients with any operative complication as the numerator and the number of patients undergoing surgical treatment as the denominator.	Postoperative 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative mortality rate	Mortality will be calculated as the ratio between the number of patients who died as numerator and number of all patients undergoing surgical treatment as the denominator.	Postoperative 30 days
R0 resection rate	Number of patients underwent gastrectomy for the denominator, number of R0 resection patients is numerator, the ratio is the R0 resection rate. The definition of R0 resection is according to the Japanese gastric cancer treatment guidelines 2014 (ver. 4)（Gastric Cancer. 2017 Jan;20(1):1-19.）.	The day of surgery
Completion rate of laparoscopic surgery	Ratio will be calculated with the number of patients complete the laparoscopic gastrectomy as the numerator, and number of all patients undergoing laparoscopic surgical treatment as the denominator.	The day of surgery

Collaborators and Investigators

• Sponsor: West China Hospital
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Fudan University; Shanghai Zhongshan Hospital; Chinese PLA General Hospital; RenJi Hospital; Southwest Hospital, China; Peking University Cancer Hospital & Institute; Ruijin Hospital; Guangdong Provincial People's Hospital; The First Hospital of Jilin University; Fujian Medical University Union Hospital; Tang-Du Hospital; Sir Run Run Shaw Hospital; Southern Medical University, China; Harbin Medical University

Publications and helpful links

General Publications

• Hu Y, Huang C, Sun Y, Su X, Cao H, Hu J, Xue Y, Suo J, Tao K, He X, Wei H, Ying M, Hu W, Du X, Chen P, Liu H, Zheng C, Liu F, Yu J, Li Z, Zhao G, Chen X, Wang K, Li P, Xing J, Li G. Morbidity and Mortality of Laparoscopic Versus Open D2 Distal Gastrectomy for Advanced Gastric Cancer: A Randomized Controlled Trial. J Clin Oncol. 2016 Apr 20;34(12):1350-7. doi: 10.1200/JCO.2015.63.7215. Epub 2016 Feb 22.
• Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, Haag C, Mauer ME, Hasan B, Welch J, Ott K, Hoelscher A, Schneider PM, Bechstein W, Wilke H, Lutz MP, Nordlinger B, Van Cutsem E, Siewert JR, Schlag PM. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010 Dec 10;28(35):5210-8. doi: 10.1200/JCO.2009.26.6114. Epub 2010 Nov 8.
• Chen XZ, Yang K, Liu J, Chen XL, Hu JK. Neoadjuvant plus adjuvant chemotherapy benefits overall survival of locally advanced gastric cancer. World J Gastroenterol. 2011 Oct 28;17(40):4542-4. doi: 10.3748/wjg.v17.i40.4542.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 31, 2018
• Primary Completion (ANTICIPATED): April 30, 2020
• Study Completion (ANTICIPATED): April 30, 2023

Study Registration Dates

• First Submitted: January 23, 2018
• First Submitted That Met QC Criteria: March 15, 2018
• First Posted (ACTUAL): March 16, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 5, 2018
• Last Update Submitted That Met QC Criteria: September 1, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: neoadjuvant chemotherapy; gastric cancer; mortality; morbidity; laparoscopic gastrectomy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Postoperative Complications
• Other Study ID Numbers: CLASS-03a

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Pending

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No