Treatment Strategy for Stage IV Gastric Cancer With Positive Peritoneal Cytology as the Only Non-curable Factor

Not Applicable

• Conditions: Stomach Neoplasm
• Interventions: Procedure: standard gastrectomy with D2 lymphadenectomy; Procedure: hyperthermic intraperitoneal chemotherapy; Procedure: Extensive intraperitoneal lavage; Other: Postoperative chemotherapy; Other: Preoperative chemotherapy

• Registration Number: NCT02969122
• Lead Sponsor: Peking University

Brief Summary

Gastric cancer with positive is defined as stage IV disease in 7th AJCC/UICC TNM staging system. Controversy exists on the treatment of this part of patients. This trial aimed to explore the optimal treatment strategy for stage IV gastric cancer with positive peritoneal cytology as the only non-curable factor.

Detailed Description

In the 7th AJCC/UICC TNM staging system, gastric cancer with positive peritoneal cytology (CY+) is defined as stage IV disease. In NCCN clinical practice guidelines, it is suggested that positive peritoneal cytology in the absence of visible peritoneal implants should be considered as M1 disease and surgery as initial treatment is not recommended for patients with positive peritoneal cytology. However, in the Japanese gastric cancer treatment guidelines 2014, it is suggested that standard gastrectomy can be proposed for patients with no other non-curative factors and if the CY+ status was revealed after surgery, postoperative treatment with S-1 can be recommended as the tentative standard. Previous studies have also proved that extensive intraperitoneal lavage(EIPL) and Hyperthermic Intraperitoneal Chemotherapy(HIPEC) are effective methods for the treatment of peritoneal metastasis.

In order to optimize the treatment strategy of this part of patients, this trial is designed to compare the effectiveness of 2 treatment strategies.

Study Timeline

• Status Verified: 2016-11
• Study Start: 2016-11
• Study First Submitted: 2016-11-12
• Study First Submitted QC: 2016-11-16
• Study First Posted: 2016-11-21
• Last Update Submitted: 2016-11-23
• Last Update Posted: 2016-11-28
• Primary Completion: 2023-12
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 59

Inclusion Criteria

• Pathologically diagnosed gastric adenocarcinoma with endoscopic biopsy;
• Pretreatment clinical stage with computed tomography and/or endoscopic ultrasonography;
• Clinical stage cT2-4 N0-3 M0;
• Standard gastrectomy with D2 lymphadenectomy is needed according to the clinicians' evaluation;
• ECOG performance score ≤2, with tolerance of standard gastrectomy and D2 lymphadenectomy;
• Positive peritoneal cytology;
• Signed informed consent.

Exclusion Criteria

• Remnant gastric cancer, recurrence gastric cancer or multi-primary cancers;
• Intraoperative identified other unresectable factors including other metastasis except positive peritoneal cytology;
• Postoperative pathologically diagnosed as non adenocarcinoma;
• Pregnant or lactate women;
• Child-bearing period adults who refuse to birth control during the trial;
• Uncontrolled epilepsy, CNS disease or mental disorder that may influence the compliance of the patient;
• Severe/active heart disease, including but not limited to acute coronary syndrome, congestive heart failure with less than NYHA II cardiac function, severe arrhythmia that needs drug control, cardiac infarction within 12 month;
• Organ transplantation patients who needs immune suppression therapy;
• Patients who needs emergency surgery because of bleeding, perforation or obstruction.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Surgery-first	standard gastrectomy with D2 lymphadenectomy	Patients in this arm will receive standard gastrectomy with D2 lymphadenectomy after randomization. Hyperthermic intraperitoneal chemotherapy (HIPEC) and extensive intraperitoneal lavage (EIPL) will be applied before abdominal closure. After surgery, 8 cycles of postoperative chemotherapy will be performed.
Surgery-first	Postoperative chemotherapy	Patients in this arm will receive standard gastrectomy with D2 lymphadenectomy after randomization. Hyperthermic intraperitoneal chemotherapy (HIPEC) and extensive intraperitoneal lavage (EIPL) will be applied before abdominal closure. After surgery, 8 cycles of postoperative chemotherapy will be performed.
Surgery-first	hyperthermic intraperitoneal chemotherapy	Patients in this arm will receive standard gastrectomy with D2 lymphadenectomy after randomization. Hyperthermic intraperitoneal chemotherapy (HIPEC) and extensive intraperitoneal lavage (EIPL) will be applied before abdominal closure. After surgery, 8 cycles of postoperative chemotherapy will be performed.
Chemotherapy-first	Extensive intraperitoneal lavage	Patients will receive hyperthermic intraperitoneal chemotherapy (HIPEC) during laparoscopic staging. Then 3 cycles of preoperative chemotherapy and clinical evaluation of chemotherapy will be performed. If the patient's disease is evaluated as progressed, the patient will receive systemic therapy. If it's stable or remission, a second time laparoscopic staging and peritoneal cytology examination will be performed. If peritoneal implant is observed, the patients will receive systemic therapy. If the peritoneal cytology is still positive, the treatment will be decided according to the suggestion of MDT discussion. If the peritoneal cytology is converted negative, standard gastrectomy with D2 lymphadenectomy and extensive intraperitoneal lavage (EIPL) will be performed. Postoperative chemotherapy will be determined according to the pathological evaluation of preoperative chemotherapy response.
Surgery-first	Extensive intraperitoneal lavage	Patients in this arm will receive standard gastrectomy with D2 lymphadenectomy after randomization. Hyperthermic intraperitoneal chemotherapy (HIPEC) and extensive intraperitoneal lavage (EIPL) will be applied before abdominal closure. After surgery, 8 cycles of postoperative chemotherapy will be performed.
Chemotherapy-first	standard gastrectomy with D2 lymphadenectomy	Patients will receive hyperthermic intraperitoneal chemotherapy (HIPEC) during laparoscopic staging. Then 3 cycles of preoperative chemotherapy and clinical evaluation of chemotherapy will be performed. If the patient's disease is evaluated as progressed, the patient will receive systemic therapy. If it's stable or remission, a second time laparoscopic staging and peritoneal cytology examination will be performed. If peritoneal implant is observed, the patients will receive systemic therapy. If the peritoneal cytology is still positive, the treatment will be decided according to the suggestion of MDT discussion. If the peritoneal cytology is converted negative, standard gastrectomy with D2 lymphadenectomy and extensive intraperitoneal lavage (EIPL) will be performed. Postoperative chemotherapy will be determined according to the pathological evaluation of preoperative chemotherapy response.
Chemotherapy-first	hyperthermic intraperitoneal chemotherapy	Patients will receive hyperthermic intraperitoneal chemotherapy (HIPEC) during laparoscopic staging. Then 3 cycles of preoperative chemotherapy and clinical evaluation of chemotherapy will be performed. If the patient's disease is evaluated as progressed, the patient will receive systemic therapy. If it's stable or remission, a second time laparoscopic staging and peritoneal cytology examination will be performed. If peritoneal implant is observed, the patients will receive systemic therapy. If the peritoneal cytology is still positive, the treatment will be decided according to the suggestion of MDT discussion. If the peritoneal cytology is converted negative, standard gastrectomy with D2 lymphadenectomy and extensive intraperitoneal lavage (EIPL) will be performed. Postoperative chemotherapy will be determined according to the pathological evaluation of preoperative chemotherapy response.
Chemotherapy-first	Preoperative chemotherapy	Patients will receive hyperthermic intraperitoneal chemotherapy (HIPEC) during laparoscopic staging. Then 3 cycles of preoperative chemotherapy and clinical evaluation of chemotherapy will be performed. If the patient's disease is evaluated as progressed, the patient will receive systemic therapy. If it's stable or remission, a second time laparoscopic staging and peritoneal cytology examination will be performed. If peritoneal implant is observed, the patients will receive systemic therapy. If the peritoneal cytology is still positive, the treatment will be decided according to the suggestion of MDT discussion. If the peritoneal cytology is converted negative, standard gastrectomy with D2 lymphadenectomy and extensive intraperitoneal lavage (EIPL) will be performed. Postoperative chemotherapy will be determined according to the pathological evaluation of preoperative chemotherapy response.
Chemotherapy-first	Postoperative chemotherapy	Patients will receive hyperthermic intraperitoneal chemotherapy (HIPEC) during laparoscopic staging. Then 3 cycles of preoperative chemotherapy and clinical evaluation of chemotherapy will be performed. If the patient's disease is evaluated as progressed, the patient will receive systemic therapy. If it's stable or remission, a second time laparoscopic staging and peritoneal cytology examination will be performed. If peritoneal implant is observed, the patients will receive systemic therapy. If the peritoneal cytology is still positive, the treatment will be decided according to the suggestion of MDT discussion. If the peritoneal cytology is converted negative, standard gastrectomy with D2 lymphadenectomy and extensive intraperitoneal lavage (EIPL) will be performed. Postoperative chemotherapy will be determined according to the pathological evaluation of preoperative chemotherapy response.

Primary Outcome Measures

Name	Time	Method
Overall survival	3 year

Secondary Outcome Measures

Name	Time	Method
peritoneal recurrence rate	3 year
morbidity and mortality of HIPEC and EIPL	30 days after HIPEC and EIPL procedures
rate of peritoneal cytology converted to negative	7 days After the second time laparoscopic staging and peritoneal cytology examination
Recurrence free survival	3 year

Trial Locations

Locations (1)

Gastrointestinal Cancer Center, Peking University Cancer Hospital; 🇨🇳 Beijing, Beijing, China