Randomized Controlled Trial on Effect of Lymph Node Mapping by Indocyanine Green Via Submucosal or Subserosal Injection

Gastric Cancer Clinical Trial

Official title:

Comparison of Submucosal and Subserosal Approaches Toward Optimized Indocyanine Green Tracer-Guided Laparoscopic Lymphadenectomy for Patients With Gastric Cancer: The FUGES-019 Randomized Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04219332
• Other study ID #: FUGES-019
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 31, 2019
• Est. completion date: October 28, 2023

Study information

• Verified date: October 2023
• Source: Fujian Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to evaluate whether submucosal or subserous injection of indocyanine green during laparoscopic lymphadenectomy for patients with gastric cancer was different. The patients with gastric adenocarcinoma (cT1-4a, N0/+, M0) were studied.

Description:

In recent years, with the successful application of ICG (indocyanine green) fluorescence imaging technology in laparoscopic equipment, scholars have found that ICG near-infrared imaging has better tissue penetration and can better identify lymph nodes in hypertrophic adipose tissue than other dyes under visible light, which makes ICG fluorescence imaging guide laparoscopic radical resection of gastric cancer lymph node dissection has become a new exploration direction. ICG near-infrared imaging technology has important research value, good application prospects, and broad development space in laparoscopic radical resection of gastric cancer. However, at present, the application of ICG near-infrared imaging technology in laparoscopic radical resection of gastric cancer is still in the exploratory stage, and there is no unified standard. Therefore, in the world, there is still a lack of high-level evidence-based evidence of large-sample prospective randomized controlled trials to evaluate the effectiveness, safety, and feasibility of submucosal or subserous injection of ICG in guiding laparoscopic D2 resection of gastric cancer. The investigator first carried out this study in the world to evaluate the lymph node dissection and perioperative safety of gastric cancer patients who received a submucosal injection of ICG and subserous injection of ICG during laparoscopic radical gastrectomy in the same period, to promote the standardized development of ICG near-infrared imaging in laparoscopic radical gastrectomy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 266
• Est. completion date: October 28, 2023
• Est. primary completion date: November 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria:

1. Age from 18 to 75 years

2. Primary gastric adenocarcinoma (papillary, tubular, mucinous, signet ring cell, or poorly differentiated) confirmed pathologically by endoscopic biopsy

3. Clinical stage tumor T1-4a (cT1-4a), N0/+, M0 at preoperative evaluation according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual Eighth Edition. Preoperative staging was made by conducting mandatory computed tomography (CT) scans and an optional endoscopic ultrasound

4. No distant metastasis, no direct invasion of pancreas, spleen or other organs nearby in the preoperative examinations

5. Performance status of 0 or 1 on Eastern Cooperative Oncology Group scale (ECOG)

6. American Society of Anesthesiology score (ASA) class I, II, or III

7. Written informed consent

Exclusion criteria:

1. Women during pregnancy or breast-feeding

2. Severe mental disorder

3. History of previous upper abdominal surgery (except laparoscopic cholecystectomy)

4. History of previous gastrectomy, endoscopic mucosal resection or endoscopic submucosal dissection

5. Rejection of laparoscopic resection

6. History of allergy to iodine agents

7. Enlarged or bulky regional lymph node diameter over 3cm by preoperative imaging

8. History of other malignant disease within past five years

9. History of previous neoadjuvant chemotherapy or radiotherapy

10. History of unstable angina or myocardial infarction within past six months

11. History of cerebrovascular accident within past six months

12. History of continuous systematic administration of corticosteroids within one month

13. Requirement of simultaneous surgery for other disease

14. Emergency surgery due to complication (bleeding, obstruction or perforation) caused by gastric cancer

15. Forced expiratory volume in 1 second (FEV1)<50% of predicted values

16. Linitis plastica, Widespread

Related Conditions & MeSH terms

• Gastric Cancer
• Indocyanine Green
• Injection Site
• Stomach Neoplasms

Intervention

Drug:
• Subserosa injection of indocyanine green
After preoperative exploration, the indocyanine green powder (Dandong Yichuang Pharmaceutical Co) is dissolved in 0.5 mg/ml of sterile water and the prepared solution (1.5 ml for each point) is injected along the subserosal of the stomach at 6 specific points along the lesser and greater curvature of the stomach.
• submucosal injection of indocyanine green
One day before surgery, 1.25 mg/ml indocyanine green (Dandong Yichuang Pharmaceutical Co) was prepared in sterile water and 0.5 ml of the solution was injected into the submucosal layer at 4 quadrants around the primary tumor, amounting to 2.5 mg of indocyanine green.

Locations

Country	Name	City	State
China	Department of Gastric Surgery	Fuzhou	Fujian

Sponsors (1)

Lead Sponsor	Collaborator
Fujian Medical University

Country where clinical trial is conducted

China, 

References & Publications (9)

Bredart A, Bottomley A, Blazeby JM, Conroy T, Coens C, D'Haese S, Chie WC, Hammerlid E, Arraras JI, Efficace F, Rodary C, Schraub S, Costantini M, Costantini A, Joly F, Sezer O, Razavi D, Mehlitz M, Bielska-Lasota M, Aaronson NK; European Organisation for Research and Treatment of Cancer Quality of Life Group and Quality of Life Unit. An international prospective study of the EORTC cancer in-patient satisfaction with care measure (EORTC IN-PATSAT32). Eur J Cancer. 2005 Sep;41(14):2120-31. doi: 10.1016/j.ejca.2005.04.041. — View Citation

Chen QY, Xie JW, Zhong Q, Wang JB, Lin JX, Lu J, Cao LL, Lin M, Tu RH, Huang ZN, Lin JL, Zheng HL, Li P, Zheng CH, Huang CM. Safety and Efficacy of Indocyanine Green Tracer-Guided Lymph Node Dissection During Laparoscopic Radical Gastrectomy in Patients With Gastric Cancer: A Randomized Clinical Trial. JAMA Surg. 2020 Apr 1;155(4):300-311. doi: 10.1001/jamasurg.2019.6033. — View Citation

Chen QY, Zhong Q, Liu ZY, Xie JW, Wang JB, Lin JX, Lu J, Cao LL, Lin M, Tu RH, Huang ZN, Lin JL, Li P, Zheng CH, Huang CM. Does Noncompliance in Lymph Node Dissection Affect Oncological Efficacy in Gastric Cancer Patients Undergoing Radical Gastrectomy? Ann Surg Oncol. 2019 Jun;26(6):1759-1771. doi: 10.1245/s10434-019-07217-x. Epub 2019 Feb 12. — View Citation

Cianchi F, Indennitate G, Paoli B, Ortolani M, Lami G, Manetti N, Tarantino O, Messeri S, Foppa C, Badii B, Novelli L, Skalamera I, Nelli T, Coratti F, Perigli G, Staderini F. The Clinical Value of Fluorescent Lymphography with Indocyanine Green During Robotic Surgery for Gastric Cancer: a Matched Cohort Study. J Gastrointest Surg. 2020 Oct;24(10):2197-2203. doi: 10.1007/s11605-019-04382-y. Epub 2019 Sep 4. — View Citation

Herrera-Almario G, Patane M, Sarkaria I, Strong VE. Initial report of near-infrared fluorescence imaging as an intraoperative adjunct for lymph node harvesting during robot-assisted laparoscopic gastrectomy. J Surg Oncol. 2016 Jun;113(7):768-70. doi: 10.1002/jso.24226. Epub 2016 Mar 29. — View Citation

Kwon IG, Son T, Kim HI, Hyung WJ. Fluorescent Lymphography-Guided Lymphadenectomy During Robotic Radical Gastrectomy for Gastric Cancer. JAMA Surg. 2019 Feb 1;154(2):150-158. doi: 10.1001/jamasurg.2018.4267. — View Citation

Lee JH, Ryu KW, Kim CG, Kim SK, Choi IJ, Kim YW, Chang HJ, Bae JM, Hong EK. Comparative study of the subserosal versus submucosal dye injection method for sentinel node biopsy in gastric cancer. Eur J Surg Oncol. 2005 Nov;31(9):965-8. doi: 10.1016/j.ejso.2005.03.006. — View Citation

Tajima Y, Yamazaki K, Masuda Y, Kato M, Yasuda D, Aoki T, Kato T, Murakami M, Miwa M, Kusano M. Sentinel node mapping guided by indocyanine green fluorescence imaging in gastric cancer. Ann Surg. 2009 Jan;249(1):58-62. doi: 10.1097/SLA.0b013e3181927267. — View Citation

Wilson MR, Poolton JM, Malhotra N, Ngo K, Bright E, Masters RS. Development and validation of a surgical workload measure: the surgery task load index (SURG-TLX). World J Surg. 2011 Sep;35(9):1961-9. doi: 10.1007/s00268-011-1141-4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Number of Retrieved Lymph Nodes	Total Number of Retrieved Lymph Nodes	One month after surgery
Secondary	Total number of fluorescent lymph nodes in groups A and B	Total number of fluorescent lymph nodes in groups A and B	One month after surgery
Secondary	Relationship between fluorescent lymph nodes and positive lymph nodes in groups A and B (true positive rate)	Relationship between fluorescent lymph nodes and positive lymph nodes in groups A and B (true positive rate)	One month after surgery
Secondary	Relationship between fluorescent lymph nodes and negative lymph nodes in groups A and B (false positive rate)	Relationship between fluorescent lymph nodes and negative lymph nodes in groups A and B (false positive rate)	One month after surgery
Secondary	Relationship between non-fluorescent and negative lymph nodes in groups A and B (true negative rate)	Relationship between non-fluorescent and negative lymph nodes in groups A and B (true negative rate)	One month after surgery
Secondary	Relationship between non-fluorescent lymph nodes and positive lymph nodes in groups A and B (false negative rate)	Relationship between non-fluorescent lymph nodes and positive lymph nodes in groups A and B (false negative rate)	One month after surgery
Secondary	Number of Metastasis Lymph Nodes	Number of Metastasis Lymph Nodes	One month after surgery
Secondary	Metastasis rate of lymph node	Metastasis rate of lymph node	One month after surgery
Secondary	Mortality rates	This is for the early mortality, which defined as the event observed within 30 days after surgery.	30 days
Secondary	Morbidity rates	This is for the incidence of early postoperative complications, which defined as the event observed within 30 days after surgery.	30 days
Secondary	3-year disease free survival rate	Disease-free survival is calculated from the day of surgery to the day of recurrence or death (When the specific date of recurrence of the tumor is unknown, the endpoint is the date of death due to tumor causes). If neither death nor recurrence of the tumor is observed, the endpoint is the final date that a patient is confirmed as relapse-free. (The final date of DFS: The last date of the outpatient visit day or the date of acceptance of the examination).	36 months
Secondary	3-year recurrence pattern	Recurrence patterns are classified into five categories at the time of first diagnosis: locoregional, hematogenous, peritoneal, distant lymph node, and mixed type.	36 months
Secondary	Time to first ambulation	Time to first ambulation in hours is used to assess the postoperative recovery course.	30 days
Secondary	Time to first flatus	Time to first flatus in days is used to assess the postoperative recovery course.	30 days
Secondary	Time to first liquid diet	Time to first liquid diet in days is used to assess the postoperative recovery course.	30 days
Secondary	Time to first soft diet	Time to first soft diet in days is used to assess the postoperative recovery course.	30 days
Secondary	Duration of postoperative hospital stay	Duration of postoperative hospital stay in days is used to assess the postoperative recovery course.	30 days
Secondary	The variation of weight	The variation of weight on postoperative 3, 6, 9 and 12 months are used to access the postoperative nutritional status and quality of life.	3, 6, 9 and 12 months
Secondary	The variation of BMI in kg/m^2	The variation of BMI in kg/m^2 on postoperative 3, 6, 9 and 12 months are used to access the postoperative nutritional status and quality of life.	3, 6, 9 and 12 months
Secondary	Intraoperative morbidity rates	The intraoperative postoperative morbidity rates are defined as the rates of event observed within operation.	1 day
Secondary	The variation of white blood cell count	The values of white blood cell count from peripheral blood before operation and on postoperative day 1, 3, 5 are recorded to access the inflammatory and immune response.	Preoperative 3 days and postoperative 1, 3, and 5 days
Secondary	The variation of hemoglobin	The values of hemoglobin in gram/liter from peripheral blood before operation and on postoperative day 1, 3, 5 are recorded to access the inflammatory and immune response.	Preoperative 3 days and postoperative 1, 3, and 5 days
Secondary	The variation of C-reactive protein	The values of C-reactive protein IN milligram/liter from peripheral blood before operation and on postoperative day 1, 3, 5 are recorded to access the inflammatory and immune response.	Preoperative 3 days and postoperative 1, 3, and 5 days
Secondary	Lymph node noncompliance rate	Lymph node noncompliance was defined as the absence of lymph nodes that should have been excised from more than 1 lymph node station. Major lymph node noncompliance was defined as more than 2 intended lymph node stations that were not removed.	1 day
Secondary	Modified EORTC cancer in-patient satisfaction with care measure (EORTC IN-PATSAT14)	Participants were asked to complete one modified European Organisation for Research and Treatment of Cancer (EORTC) IN-PATSAT14 questionnaire before their discharge from hospital.	30 days
Secondary	The Surgery Task Load Index (SURG-TLX)	Surgeons were required to complete one modified SURG-TLX questionnaire for each procedure.	1 day
Secondary	3-year overall survival rate	The overall survival is calculated from the day of surgery until death or until the final follow-up date, whichever occurs first. For survival cases, the endpoint is the last date that survival was confirmed. If the loss to follow-up occurred, the endpoint is the final date that survival could be confirmed.	36 months