Hyperthermic Intraperitoneal Chemotherapy for Advanced Gastric Cancer With Peritoneal Metastatis

Study Overview
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Brief Summary
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The incidence rate of gastric cancer is high in Southeast Asia, so is the mortality rate.Due to the lack of specific performance, about 5%-20% of patients have found peritoneal metastases at the time of first diagnosis.At present, clinical studies on HIPEC in the treatment of patients with advanced gastric cancer peritoneal metastasis are almost related to abdominal perfusion after laparoscopic gastrectomy.Herein, we conduct a single-centre randomized controlled trial to explore the safety and feasibility of laparoscopic exploration combined with HIPEC in the treatment of advanced gastric cancer with peritoneal metastasis.

Detailed Description
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Gastric cancer is one of the most common digestive tumors in the world.In China, advanced gastric cancer with severe local progression or distant metastasis is more common.Gastric cancer with peritoneal carcinomatosis has an extremely poor prognosis,with a median survival of less than 6 months.Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is currently a treatment for malignant tumors in the abdominal cavity and prevents tumor recurrence and metastasis.Studies have shown that hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) has good clinical efficacy in the prevention and treatment of peritoneal metastasis of gastric cancer and its associated malignant ascites.Therefore,we conduct a single-centre randomized controlled trial to explore the safety and feasibility of HIPEC in the treatment of advanced gastric cancer with peritoneal metastasis. The metahnism of HIPEC is taking advantage of the difference in temperature sensitivity between cancer cells and normal cells. Perfusion of the abdominal cavity with a chemical fluid of the appropriate temperature can be performed. Suitable high temperatures can directly kill tumor cells.It is generally believed that the optimal temperature for the treatment of tumors is 42.5°C to 44°C.In this study,we set the temperature 43°C. Paclitaxel is a novel broad-spectrum antitumor drug,which has a unique anti-cancer mechanism.We use Paclitaxel as peritoneal hyperthermic perfusion chemotherapy drugs.The chemotherapy is SOX(Teggio and Oxaliplatin),.The primary endpoint is PFS. Secondary endpoints are one-year OS、canversion rate and ascites assessment. A phase III study PHOENIX-GC trial had finished enrollment,and the conclusion was the median OS 17.7 and 15.2 months respectively for IP and SP.The primary analysis did not show the statistical superiority of the IP regimen.The sensitivity analysis IP considering the imbalance of ascites, suggested clinical efficacy of IP PTX in gastric cancer with peritoneal metastasis. For this reason,we conduct a trial to explore the safety and feasibility of HIPEC in the treatment of advanced gastric cancer with peritoneal metastasis.

Official Title
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A Randomized Controlled Clinical Trial of Hyperthermic Intraperitoneal Chemotherapy for Advanced Gastric Cancer With Peritoneal Metastatis

Conditions
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Stage IV Gastric Cancer With Metastasis, Hyperthermic Intraperitoneal Chemotherapy, Exploratory Behavior

Intervention / Treatment
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* Drug: Hyperthermic Intraperitoneal Chemotherapy
* Drug: Without Hyperthermic Intraperitoneal Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary gastric adenocarcinoma diagnosed pathologically by endoscopic biopsy； Laparoscopic exploration of patients with advanced gastric adenocarcinoma of peritoneal metastasis； Eastern Cooperative Oncology Group (ECOG): 0 ot 1； American Society of Anesthesiologists （ASA） score: I to Ⅲ； Patient informed consent。 Exclusion Criteria: Pregnancy or female in suckling period； Severe mental illness； Preoperative imaging or intraoperative exploration reveals distant blood, liver, lung, and brain metastases； 5 years of history of other malignant diseases； A history of unstable angina or myocardial infarction within 6 months； History of cerebral infarction or cerebral hemorrhage within 6 months； A history of sustained systemic corticosteroid treatment within 1 month； Emergency operation due to complication (bleeding, perforation or obstruction) caused by primary tumor； Pulmonary function test FEV1 <predicted value 50%。

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIPEC and chemotherapy<br>Hyperthermic Intraperitoneal Chemotherapy and SOX（Tiggio+Oxaliplatin ） | Drug: Hyperthermic Intraperitoneal Chemotherapy<br>* The investigators use Paclitaxel as peritoneal hyperthermic perfusion chemotherapy drugs，75mg/m2 for the first time，50mg/m2 for the second time and third time.The chemotherapy is SOX(Tiggio d1-d14 bid po and Oxaliplatin 130mg/m2 ivd d1 qd).The Tiggio dosage depends on the patient's body surface area, body surface area <1.25m2 40mg/time, 1.25-1.50m2 50mg/time, >1.50m2 60mg/time.<br>|
| Sham Comparator: Without HIPEC<br>Without Hyperthermic Intraperitoneal Chemotherapy，Only SOX（Tiggio+Oxaliplatin ） | Drug: Without Hyperthermic Intraperitoneal Chemotherapy<br>* The chemotherapy is SOX(Tiggio d1-d14 bid po and Oxaliplatin 130mg/m2 ivd d1 qd).The Tiggio dosage depends on the patient's body surface area, body surface area <1.25m2 40mg/time, 1.25-1.50m2 50mg/time, >1.50m2 60mg/time.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-free survival | From date of randomization until the date of first documented progression or date of death for tumor cause, whichever came first, assessed 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year survival | 1-year overall survival rate | one year | 
| Ascites assessment | Ascites assessment during surgery | Intraoperative | 
| Median survival | Median Survival Time | From date of randomization until only 50% of individuals living for tumor cause, assessed 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peritoneal metastatis, Hyperthermic Intraperitoneal Chemotherapy, Advanced gastric adenocarcinoma