Cytoreductive Surgery Combined With HIPEC and Chemotherapy for Gastric Cancer With Peritoneal Metastasis

Sponsor

Nanfang Hospital of Southern Medical University (Other)

Overall Status

Unknown status

CT.gov ID

NCT03023436

Collaborator

(none)

220

Enrollment

Locations

Arm

Duration (Months)

16.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluates the survival benefit and safety of cytoreductive surgery(CRS) combined with HIPEC and chemotherapy in gastric cancer with peritoneal metastasis.

Condition or Disease	Intervention/Treatment	Phase
Stomach Neoplasm	Procedure: Cytoreductive surgery Procedure: Hyperthermic Intraperitoneal Chemotherapy Drug: Fluoropyrimidine Drug: Cisplatin	Phase 3

Detailed Description

Peritoneal metastasis is one of the most frequent non-curable factors in advanced gastric cancer with poor prognosis, the median survival time of patients is less than 1 year and even worse in China. Recently, several new modalities have been developed and reported to improve survival, including the new chemotherapeutic agents, molecular targeting agents and hyperthermic intraperitoneal chemotherapy（HIPEC）.Still, the long-term outcomes based on multicenter randomized clinical trials (RCTs) are awaited.

The surgical approach to metastatic lesions has been proved to play a very crucial role in prolonging the survival of metastatic colorectal patients, which might be able to cure patients with the operation aiming at R0 resection. For patients with metastatic gastric cancer, surgical intervention of primary tumor and measurable metastatic lesion is technically feasible, while the survival benefit is controversial. Even though the REGATTA trial demonstrated that the removal of the primary tumor is not necessarily beneficial, the role of operation aiming at R0 resection combined with new regimens like HIPEC and new chemotherapeutic agents is still confusing and new categories of classification for metastatic gastric cancer based on the treatment response is needed.

In order to evaluate the survival benefit and safety of cytoreductive surgery(CRS) and HIPEC before beginning chemotherapy in gastric cancer with peritoneal metastasis, patients who fulfill the inclusion and exclusion criteria will be recruited in this study and receive CRS, HIPEC and chemotherapy. Chemotherapy regimen based on cisplatin and fluorouracil(CF) are recommended. Patients are followed up for 2 years and the safety and survival outcome will be analyzed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

220 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Cytoreductive Surgery Combined With Hyperthermic Intraperitoneal Chemotherapy and Systemic Chemotherapy in Gastric Cancer With Regional Peritoneal Metastasis, a Multicenter and Single-arm Phase III Study

Study Start Date :

Jan 1, 2016

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CRS + HIPEC + Systemic Chemotherapy Cytoreductive surgery(CRS) followed by Hyperthermic Intraperitoneal Chemotherapy(HIPEC) and systemic chemotherapy will be performed for the treatment of patients assigned to this group. CF regimens or other first line regimens based on Fluoropyrimidine and Cisplatin according to the National Comprehensive Cancer Network（NCCN） Guidelines （Gastric Cancer，version 3.2016) are recommended.Regimens and dosing schedules are not limited in this trial.	Procedure: Cytoreductive surgery Gastrectomy with D2 lymph node dissection and Metastasectomy for peritoneal metastatic sites only. A total, distal, or proximal gastrectomy and the type of reconstruction will be selected according to the surgeon's experience. Metastasectomy is limited to peritoneal metastatic sites only to render the patient no evidence of disease (NED) with at least 1cm negative margins when possible. Other Names: CRS , Cytoreduction Surgical Procedures Procedure: Hyperthermic Intraperitoneal Chemotherapy Docetaxel 120 mg diluted in 5.0 L of saline is forced into the abdomen through the inflow catheter by a pump and pulled out through the drains as a heated intraperitoneal perfusion.A heat exchanger keeps the intraperitoneal fluid at 43±0.5℃ and duration limited to 70 minutes.24 hours after cytoreductive surgery no less than 2 cycles postoperative chemotherapy will be recommended. Other Names: HIPEC Drug: Fluoropyrimidine CF regimens or other first line regimens based on Fluoropyrimidine and Platinum according to the NCCN Guidelines（Gastric Cancer，version 3.2016) are recommended.Regimens and dosing schedules are not limited in this trial. Other Names: fluorouracil or capecitabine Drug: Cisplatin CF regimens or other first line regimens based on Fluoropyrimidine and Platinum according to the NCCN Guidelines（Gastric Cancer，version 3.2016) are recommended.Regimens and dosing schedules are not limited in this trial. Other Names: cis-diamine dichloroplatinum(CDDP)

Arm

Intervention/Treatment

Experimental: CRS + HIPEC + Systemic Chemotherapy

Cytoreductive surgery(CRS) followed by Hyperthermic Intraperitoneal Chemotherapy(HIPEC) and systemic chemotherapy will be performed for the treatment of patients assigned to this group. CF regimens or other first line regimens based on Fluoropyrimidine and Cisplatin according to the National Comprehensive Cancer Network（NCCN） Guidelines （Gastric Cancer，version 3.2016) are recommended.Regimens and dosing schedules are not limited in this trial.

Procedure: Cytoreductive surgery

Gastrectomy with D2 lymph node dissection and Metastasectomy for peritoneal metastatic sites only. A total, distal, or proximal gastrectomy and the type of reconstruction will be selected according to the surgeon's experience. Metastasectomy is limited to peritoneal metastatic sites only to render the patient no evidence of disease (NED) with at least 1cm negative margins when possible.

Other Names:

CRS , Cytoreduction Surgical Procedures

Procedure: Hyperthermic Intraperitoneal Chemotherapy

Docetaxel 120 mg diluted in 5.0 L of saline is forced into the abdomen through the inflow catheter by a pump and pulled out through the drains as a heated intraperitoneal perfusion.A heat exchanger keeps the intraperitoneal fluid at 43±0.5℃ and duration limited to 70 minutes.24 hours after cytoreductive surgery no less than 2 cycles postoperative chemotherapy will be recommended.

Other Names:

HIPEC

Drug: Fluoropyrimidine

CF regimens or other first line regimens based on Fluoropyrimidine and Platinum according to the NCCN Guidelines（Gastric Cancer，version 3.2016) are recommended.Regimens and dosing schedules are not limited in this trial.

Other Names:

fluorouracil or capecitabine

Drug: Cisplatin

Other Names:

cis-diamine dichloroplatinum(CDDP)

Outcome Measures

Primary Outcome Measures

2-year Median survival time [24 months]
The time point when the cumulative survival rate is 50% according to the survival curve.

Secondary Outcome Measures

2-year overall survival rate [24 months]
Overall survival rate calculated according to the survival curve.
Progression free survival rate [24 months]
Progression free survival rate calculated according to the disease progression curve.
Morbidity and mortality [30 days; 24 months]
The early complication and mortality are defined as the event observed within 30 days after intervention, while the time frame for late complication is the period beyond 30 days after intervention to the end of month 24th. Complications are ranked from grade 0-5 according to CTCAE V4.0

Other Outcome Measures

Quality of life(site-specific module for gastric cancer) [Every 6 months to 2 years]
Evaluated according to European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Stomach(EORTC QLQ-STO22)
Quality of life [Every 6 months to 2 years]
Evaluated according to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Cancer (EORTC QLQ-C30)
circulating tumor cell（CTC） alteration [Every 6 months to 2 years]
circulating tumor DNA（ctDNA）alteration [Every 3 months to 2 years]
Molecular biomarker alteration [Every 6 months to 2 years]
Molecular biomarker includes 14 genes（TP53, BAI1, THSD1, ARID2, KIAA2022, ERBB4, ZNF721, NT5E, PDE10A, CA1, NUMB, NBN, ZFYVE16 and NCAM1） according to the whole-exome sequencing results.

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 74 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age from over 18 to under 75 years
Histologically proven primary gastric adenocarcinoma confirmed pathologically by endoscopic biopsy
Diagnosed with clinical T1-4N0-3M1（distant metastases confined to peritoneum, P1）according to the American Joint Committee on Cancer(AJCC) Cancer Staging Manual Seventh Edition by laparoscopic exploration
Localized peritoneal metastasis with peritoneal cancer index(PCI) less than 20
Resection of primary tumor and metastasis is anticipated to reach the CC0 status(no residual tumor )
Performance status of 0 or 1 on Eastern Cooperative Oncology Group(ECOG) scale
Written informed consent

Exclusion Criteria:

Adenocarcinoma of esophageal-gastric junction(AEG) that requires thoracotomy
Distant metastases not confined to peritoneum, including liver (H1), para-aortic lymphnode (stations 16a1 and/or b2), lung, brain, bone and other organs
Histologically proven Human epidermal growth factor receptor 2(HER2)-neu overexpressing adenocarcinoma
History of previous neoadjuvant chemotherapy , radiotherapy or clinical trial treatment within 3 months
Contraindication for anesthesia, surgery, chemotherapeutic agents or HIPEC
Women of child-bearing potential who are pregnant or breastfeeding
History of prior/other malignancies within the 5 years prior to enrollment
Cerebrovascular accident occurred within 6 months (myocardial infarction, unstable angina, cerebral infarction, or cerebral hemorrhage)
History of continuous systematic administration of corticosteroids within one month
Requirement of simultaneous surgery for other disease
Emergency surgery due to complication (bleeding, obstruction or perforation) caused by gastric cancer
FEV1<50% of predicted values

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking University Cancer Hospital	Beijing	Beijing	China	100-142
2	Fujian Provincial Hospital	Fuzhou	Fujian	China	350-014
3	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong	China	510-060
4	Guangdong General Hospital	Guangzhou	Guangdong	China	510-080
5	Cancer Center of Guangzhou Medical University	Guangzhou	Guangdong	China	510-095
6	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong	China	510-280
7	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong	China	510-515
8	The Third Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong	China	510-630
9	The Sixth Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong	China	510-655
10	Meizhou People's Hospital	Meizhou	Guangdong	China	514-031
11	Zhongshan City People Hospital	Zhongshan	Guangdong	China	528-403
12	Zhongshan Hospital, Fudan University	Shanghai	Shanghai	China	200-032
13	West China Hospital, Sichuan University	Chengdu	Sichuan	China	610-041

Sponsors and Collaborators

Nanfang Hospital of Southern Medical University

Investigators

Principal Investigator: Guoxin Li, Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group; Nanfang Hospital, Southern Medical University, China