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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Stomach Neoplasm

Intervention / Treatment
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* Procedure: Cytoreductive surgery
* Procedure: Hyperthermic Intraperitoneal Chemotherapy
* Drug: Fluoropyrimidine
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CRS + HIPEC + Systemic Chemotherapy<br>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<br>* 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.<br>* Other names: CRS , Cytoreduction Surgical Procedures;Procedure: Hyperthermic Intraperitoneal Chemotherapy<br>* 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.<br>* Other names: HIPEC;Drug: Fluoropyrimidine<br>* 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.<br>* Other names: fluorouracil or capecitabine;Drug: Cisplatin<br>* 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.<br>* Other names: cis-diamine dichloroplatinum(CDDP);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year Median survival time | The time point when the cumulative survival rate is 50% according to the survival curve. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year overall survival rate | Overall survival rate calculated according to the survival curve. | 24 months | 
| Progression free survival rate | Progression free survival rate calculated according to the disease progression curve. | 24 months | 
| Morbidity and mortality | 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 | 30 days; 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stomach Neoplasms, Cytoreduction Surgical Procedures