Clinical trial NCT03468712: Laparoscopic D2 Distal Gastrectomy Following Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancers
Official title: Laparoscopic D2 Distal Gastrectomy Following Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancers: A Prospective Multicenter Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Complications, Postoperative
Surgery--Complications
Cancer of Stomach
Chemotherapy Effect
Keywords: mortality
morbidity
neoadjuvant chemotherapy
laparoscopic gastrectomy
gastric cancer
Lead sponsor: West China Hospital
Sponsor class: OTHER
Collaborators: name: Peking University Cancer Hospital & Institute
name: Southern Medical University, China
name: Shanghai Zhongshan Hospital
name: Chinese PLA General Hospital
name: Fujian Medical University Union Hospital
name: Ruijin Hospital
name: Southwest Hospital, China
name: RenJi Hospital
name: The First Affiliated Hospital with Nanjing Medical University
name: Fudan University
name: Tang-Du Hospital
name: Harbin Medical University
name: The First Hospital of Jilin University
name: Guangdong Provincial People's Hospital
name: Sir Run Run Shaw Hospital
First posted: 2018-03-16
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Laparoscopic D2 distal gastrectomy after 3-Cycle XELOX neo-adjuvant chemotherapy
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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:

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  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.

Primary outcomes:
measure: Postoperative overall morbidity rate
timeFrame: Postoperative 30 days
Secondary outcomes:
measure: Postoperative mortality rate
timeFrame: Postoperative 30 days
measure: R0 resection rate
timeFrame: The day of surgery
measure: Completion rate of laparoscopic surgery
timeFrame: The day of surgery
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital and Institute
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Chongqing
country: China
facility: Southwest Hospital, the Third Military Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University
state: Heilonngjiang
city: Nanjing
country: China
facility: The First Affiliated Hospital with Nanjing Medical University
state: Jiangsu
city: Changchun
country: China
facility: First Hospital of Jilin University
state: Jilin
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: RenJi Hospital, Shanghai Jiaotong University
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai JiaoTong University
state: Shanghai
city: Xian
country: China
facility: Tangdu Hospital, Fourth Military Medical University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University
state: Zhejiang
Study officials:
affiliation: West China Hospital
name: Jian-Kun Hu, M.D. Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.