Clinical trial NCT02745509: Extensive Intraoperative Peritoneal Lavage After Curative Gastrectomy for Locally Advanced Gastric Cancer (SEIPLUS)
Official title: A Prospective, Multicentral, Open-label, Randomized, Controlled Clinical Trial to Investigation the Value of Extensive Intraoperative Peritoneal Lavage After Curative Gastrectomy for Locally Advanced Gastric Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gastric Cancer
Keywords: Extensive Intraoperative Peritoneal Lavage
EIPL
Gastric Cancer
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Anhui Provincial Hospital
name: The First Affiliated Hospital of Anhui Medical University
name: Anqing Municipal Hospital
name: Yuebei People's Hospital
name: The First Affiliated Hospital of Guangdong Pharmaceutical University
name: Guangdong Provincial Hospital of Traditional Chinese Medicine
name: Jiangsu Cancer Institute & Hospital
name: Jiangxi Provincial Cancer Hospital
name: Tianjin Medical University Cancer Institute and Hospital
name: First Affiliated Hospital of Wannan Medical College
name: Lishui hospital of Zhejiang University
name: Second Affiliated Hospital, School of Medicine, Zhejiang University
First posted: 2016-04-20
Enrollment: 508
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators study aims to explore the potential function of extensive intraoperative peritoneal lavage in improving the overall survival and progression-free survival for locally advanced gastric cancer after curative resection.

Hypothesis: Overall survival and progression-free survival of locally advanced gastric cancer are improved by extensive intraoperative peritoneal lavage.

Detailed description: Gastric cancer has been one of the most frequently common cancers and remains the third leading cause of death among malignant tumors all over the world. Surgery has always been considered as the most effective treatment. While significant surgical technique and perioperative management have dramatically improved the survival of patients with advanced gastric cancer, patients with T4 stage or serosal-positive gastric cancer often suffer from recurrence as peritoneal dissemination, and the prognosis of those patients is extremely poor. Despite curatively resected, Peritoneal metastasis is completed by the implantation of peritoneal free cancer cells exfoliated from serosa-invasive tumors. Therefore, things need to be done to eliminate the free exfoliated cancer cells on the peritoneal lining in order to reduce the risk of peritoneal recurrence.

A multi-institutional prospective, randomized trial has been launched by Kuramoto recently. The trail was intended to demonstrate the superiority in overall survival of addition of Extensive Intraoperative peritoneal Lavage (EIPL) to standard treatment in patients with≥T3 carcinoma of stomach. Based on the'limiting dilution theory', after total or distal gastrectomy with D2 lymphadenectomy, the peritoneal cavity is extensively rinsed 10 times with 1 L physiological saline at a time, followed by complete aspiration of the fluid. In total, 10 L saline is to be used. In this study, the EIPL-IPC group had a significantly lower incidence of peritoneal recurrence. Furthermore, the 5-year overall survival rate of the patients in the EIPL-IPC group (43.8%) was significantly better than that of the intraperitoneal chemotherapy (IPC) group (4.6%) and the surgery-alone group (0%). All in all, EIPL is easy to carry out, safe and inexpensive. Therefore, gastrectomy with EIPL will be a new standard treatment of gastric cancer.

To ensure the quality of the study, two interim analyses will be planned at the half and the completion of the study respectively. The Data and Safety Monitoring Committee will independently review the interim analysis and stop the study ahead of schedule if necessary. Furthermore, to improve the study progress and quality, the in-house interim monitoring will be performed.

Eligibility criteria: Inclusion Criteria:

1. Lower age limit of research subjects 18 years old and upper age limit of 80 years old.
2. ECOG score standard (ECOG）performance status of 0 or 1 and expected to survive more than 6 months.
3. Without any other malignancies.
4. Written informed consent from the patient.
5. Histologically proven primary gastric adenocarcinoma.
6. Patients planned for open gastrectomy.
7. Patients who have T3 (subserosal) or T4 (serosal) disease based on Ultrasound gastroscopy and intra-operative inspection with any N staging and M0 gastric cancer.
8. No preoperative neoadjuvant chemotherapy.
9. Length of esophageal invasion≤3cm and no need of thoracotomy for resection.
10. Intraoperative inclusion criteria:

    1. Clinically T3, T4a or T4b.
    2. Clinically H0 and M0. No peritoneal dissemination or Distant metastases.
    3. Possible for R0 surgery.

Exclusion Criteria:

1. Female in pregnancy or lactation.
2. Supraclavicular lymph nodes metastases，pelvis or ovarian implantation，peritoneal dissemination，liver，lung and bone metastases.
3. Massive ascites or cachexia.
4. Patients participating in any other clinical trails currently，or participated in other trails within 1 months.
5. Without a history of stomach or esophageal cancers, including stromal tumor，sarcoma，lymphoma and carcinoid.
6. Suffering from other serious diseases, including cardiovascular, respiratory, kidney, or liver disease, complicated by poorly controlled hypertension, diabetes, mental disorders or diseases.
7. Patients with poor compliance or considered to be poor compliance.

Primary outcomes:
measure: Overall survival
timeFrame: 3-year
Secondary outcomes:
measure: Disease-free survival
timeFrame: 3-year
measure: Peritoneal recurrence
timeFrame: 3-year
measure: Postoperative complications
timeFrame: an average of 10 days
measure: Post-operative quality of life
timeFrame: an average of 10 days
Other outcomes:
Locations:
city: Anqing
country: China
facility: Anqing Municipal Hospital
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Wuhu
country: China
facility: First Affiliated Hospital of Wannan Medical College
state: Anhui
city: Guangzhou
country: China
facility: Cancer Center of Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial Hospital of Traditional Chinese Medicine
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangdong Pharmaceutical University
state: Guangdong
city: Guangzhou
country: China
facility: Yuebei People's Hospital
state: Guangdong
city: Nanjing
country: China
facility: Jiangsu Cancer Institute & Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial Cancer Hospital
state: Jiangxi
city: Hangzhou
country: China
facility: Second Affiliated Hospital, School of Medicine, Zhejiang University
state: Zhejiang
city: Lishui
country: China
facility: Lishui Hospital of Zhejiang University
state: Zhejiang
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
Study officials:
References:
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citation: Guo J, Xu A, Sun X, Zhao X, Xia Y, Rao H, Zhang Y, Zhang R, Chen L, Zhang T, Li G, Xu H, Xu D. Three-year outcomes of the randomized phase III SEIPLUS trial of extensive intraoperative peritoneal lavage for locally advanced gastric cancer. Nat Commun. 2021 Nov 15;12(1):6598. doi: 10.1038/s41467-021-26778-8.
citation: Guo J, Xu A, Sun X, Zhao X, Xia Y, Rao H, Zhang Y, Zhang R, Chen L, Zhang T, Li G, Xu H, Xu D. Combined Surgery and Extensive Intraoperative Peritoneal Lavage vs Surgery Alone for Treatment of Locally Advanced Gastric Cancer: The SEIPLUS Randomized Clinical Trial. JAMA Surg. 2019 Jul 1;154(7):610-616. doi: 10.1001/jamasurg.2019.0153.