Laparoscopic Versus Open Gastrectomy for Elderly Local Advanced Gastric Cancer Patients

Laparoscopic Versus Open Gastrectomy for Elderly Local Advanced Gastric Cancer Patients: a Phase II Randomized Parallel Controlled Trial

Gastric cancer is one of the most common malignant tumors worldwide. With the rapid aging of global population, the number of elderly patients with local advanced gastric cancer is increasing. Surgery is the essential treatment for local advanced gastric cancer. However, because of the degeneration of physiological organs, cell functions, compensatory ability, immunity, and physiological reserve ability, elderly patients often face great safety issues when having surgery. Therefore, how to treat the elderly patients with local advanced gastric cancer with safe and effective surgery is one of the important problems in the field of gastric cancer treatment. With the introduction of minimally invasive treatment concepts and techniques, the role of laparoscopic radical gastrectomy in the treatment of early gastric cancer, as well as the advantages of trauma control and postoperative accelerated rehabilitation have been confirmed, however, there is still a lack of sufficient high-level clinical evidence in the elderly patients with advanced gastric cancer. The current study therefore aims to evaluate the safety and efficacy of laparoscopic versus open gastrectomy for advanced gastric cancer in elderly patients, using a randomized parallel controlled study design. The investigators hypothesized that laparoscopic gastrectomy is superior to open gastrectomy in terms of perioperative safety for local advanced gastric cancer patients aged 70 and above.

Study Overview

• Status: Recruiting
• Conditions: Advanced Gastric Cancer
• Intervention / Treatment: Procedure: Laparoscopic gastrectomy; Procedure: Open gastrectomy

Detailed Description

Gastric cancer is one of the most common cancer and cause of cancer death worldwide. With the rapid aging of global population, the number of elderly patients with local advanced gastric cancer has been continuously increasing. Surgery is the essential treatment for local advanced gastric cancer. However, elderly patients are at high risk of postoperative complications due to reduced functional reserve and increased comorbidities. Studies have shown that elder patients can have postoperative complication incidence up to 18%-32% and surgery-related mortality rate to 3.8%-9.5%. Therefore, elderly patients usually require more restrict operative injury control compared to the younger population. Surgical safety and effectiveness has become a crucial research focus for local advanced gastric cancer among elderly patients.

Laparoscopic gastrectomy is one of the standard treatments for early gastric cancer and has demonstrated its application value in local advanced gastric cancer. Two recent meta-analysis on observational studies have shown the feasibility of laparoscopic gastrectomy in elderly gastric cancer patients. Compared to conventional open resections, elderly patients may benefit from the advantages of laparoscopic approach such as less trauma, less blood loss, faster bowel movement recovery, earlier food intake, and shorter hospitalization. However, laparoscopic gastrectomy raises issues such as prolonged operation time and disturbance of circulatory and respiratory dynamics by carbon dioxide pneumoperitoneum during the procedure. Nonetheless, all currently available evidence comes from observational studies that are susceptible to bias and evidence on long-term survival is scarce. The investigators therefore proposed to conduct this randomized controlled trial comparing the feasibility and survival benefit of laparoscopic with open gastrectomy for elderly patients with local advanced gastric cancer. The investigators hypothesized that laparoscopic gastrectomy is superior to open gastrectomy in terms of perioperative safety for local advanced gastric cancer patients aged 70 and above.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fei Shan, MD; Phone Number: 0086-10-88196606; Email: shanfei@hsc.pku.edu.cn
• Study Contact Backup: Name: Ziyu Li, MD; Phone Number: 0086-10-88196605; Email: ziyu_li@hsc.pku.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Peking University Cancer Hospital & Institute
      • Sub-Investigator: Xiangji Ying, M.P.H
      • Sub-Investigator: Chao Gao, M.D.
      • Contact: Fei Shan, M.D.; Phone Number: 86-010-8819-6606; Email: shanfei@hsc.pku.edu.cn
      • Contact: Ziyu Li, M.D.; Phone Number: 86-010-8819-6605; Email: ziyu_li@hsc.pku.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ambulatory male or female aged 70 and above
• Karnofsky score≥70%
• Histologically proven gastric adenocarcinoma in biopsy (including Lauren classification) Proven clinical stage of cT2-4aNanyM0 by baseline ultrasound endoscope, enhanced CT/MRI examination, or diagnostic laparoscopy using Habermann Standards
• No past chemotherapy or radiotherapy before diagnosis
• Primary tumor located at stomach, achievable naked-eye complete resection (R0/1) via distal subtotal or total gastrectomy plus lymphadenectomy
• Haematology and biochemistry index meet the following: hemoglobin≥80g/L, absolute neutrophils count (ANC)≥1.5×109/L, platelet≥100×109/L, ALT、AST≤2.5 times the upper limit of normal value, ALP≤2.5 times the upper limit of normal value, serum total bilirubin<1.5 times the upper limit of normal value, serum creatinine<1 times the upper limit of normal value, serum albumin≥30g/L
• Heart and lung function can withstand surgery
• No severe concomitant disease that leads to survival<3 years
• Willing and able to comply with study protocol Written agreement consent before enrolment and full aware of the right to quit the study at any time with no loss

Exclusion Criteria:

• Uncontrolled seizure, central nervous system diseases, or mental disorders;
• Past history of upper abdominal surgery (except for laparoscopic cholecystectomy)
• Past history of gastric surgery (including diagnosis procedure such as ESD and EMR)
• Other malignant diseases in 5 years (except for cured skin carcinoma and cervical carcinoma in situ)
• Clinical severe or active heart diseases, such as symptomatic coronary heart disease, NYHA grade II or above congestive heart failure, severe arrhythmia, or myocardial infarction in 6 months
• Cerebral hemorrhage or infarction in 6 months
• Organ transplant recipients under immunosuppressive therapy
• Severe uncontrolled repeated infection or other severe uncontrolled concomitant diseases
• Medium or severe renal damage (creatinine clearance rate≤50ml/min or serum creatinine> upper limit of normal value)
• Other diseases requiring synchronous surgery
• Requiring emergent surgery due to oncologic emergent (e.g. bleeding, perforation, obstruction)
• FEV1<50% of expected value Participated in other studies 4 weeks before the randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Laparoscopic gastrectomy; A standard laparoscopic gastrectomy with D2 lymphadenectomy will be performed by two experienced surgeons, according to the Japanese Gastric Cancer Treatment Guidelines 2014 (version 4) and the Japanese Classification of Gastric Carcinoma (3rd English edition).	Procedure: Laparoscopic gastrectomy; Patients will receive laparoscopic gastrectomy within one week after randomization.
Active Comparator: Open gastrectomy; A standard open gastrectomy with D2 lymphadenectomy will be performed by two experienced surgeons, according to the Japanese Gastric Cancer Treatment Guidelines 2014 (version 4) and the Japanese Classification of Gastric Carcinoma (3rd English edition).	Procedure: Open gastrectomy; Patients will receive open gastrectomy within one week after randomization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative complication rate	Surgery related complications include incision complications (infection, effusion, dehiscence, poor healing), peritoneal effusion or abscess formation, hemorrhage (inside abdominal cavity, inside digestive tract), ileus, anastomotic leakage, anastomotic stenosis, intestinal fistula, lymphatic leakage, pancreatic fistula, gastroparesis, pancreatitis, lung infection, pleural effusion, urinary tract infection, renal failure, liver failure, cardio-cerebrovascular events (both lower extremities thrombosis, pulmonary embolism, myocardial infarction, arrhythmia, cerebral infarction, etc.), and others. Complications will be reported and graded according to the Clavien-Dindo classification of surgical complications.	within 30 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of postoperative hospitalization stay	Postoperative hospitalization stay refers to the time interval between the day of surgery and discharge, and will be recorded by the investigators.	within 30 days after surgery
Postoperative life quality	Will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaires (i.e. QLQ-C30), which contains both QLQ-STO22 and ELD14 modules. This is a questionnaire developed to assess the generic and disease-specific quality of life for elderly gastric cancer patients by European Organisation for Research and Treatment of Cancer. The Summary Score will be calculated from the mean of scales. Prior to calculating the mean, the symptom scales will need to be reversed to obtain a uniform direction of all scales. The summary score should only be calculated if all of the required scale scores are available (using scale scores based on the completed items, provided that at least 50% of the items in that scale have been completed.	one-year after surgery
Three-year overall survival rate	Overall survival is defined as the time interval from the time of the radical gastrectomy to the date of all-cause death or the last follow-up. Three-year overall survival rate will be calculated using the Kaplan-Meier Methods.	Three-year after surgery
Three-year disease-free survival rate	Disease-free survival is defined as the time interval from the time of the radical gastrectomy to the date of the detection of cancer recurrence or the last follow-up. Three-year disease-free survival rate will be calculated using the Kaplan-Meier Methods.	Three-year after surgery
Postoperative pain	Postoperative pain will be measured using the Numeric Rating Scale (NRS-11) which is an 11-point scale for patient self-reporting of pain. The scale ranges from 0 to 10, with 0 being no pain. Pain level will be graded into four levels for analysis: "0: No Pain", "1-3: Mild Pain", "4-6 Moderate Pain", and "7-10 Severe Pain".	within 2 weeks after surgery

Collaborators and Investigators

• Sponsor: Peking University
• Investigators: Principal Investigator: Ziyu Li, MD, Peking University Cancer Hospital and Institute

Publications and helpful links

General Publications

• Li Z, Shan F, Ying X, Xue K, Ji J. Laparoscopic versus open gastrectomy for elderly local advanced gastric cancer patients: study protocol of a phase II randomized controlled trial. BMC Cancer. 2018 Nov 16;18(1):1118. doi: 10.1186/s12885-018-5041-y.

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2018
• Primary Completion (Anticipated): July 30, 2020
• Study Completion (Anticipated): July 30, 2023

Study Registration Dates

• First Submitted: May 14, 2018
• First Submitted That Met QC Criteria: June 19, 2018
• First Posted (Actual): June 21, 2018

Study Record Updates

• Last Update Posted (Actual): September 28, 2018
• Last Update Submitted That Met QC Criteria: September 26, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Elderly patients; Laparoscopic gastrectomy; Open gastrectomy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: SF2018-4-2156

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The deidentified datasets generated during the current study will be publicly available via an appropriate data archive 6 months after the completion of the trial.
• IPD Sharing Time Frame: 6 months after the completion of the trial
• IPD Sharing Access Criteria: As request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

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