Efficacy of HIPEC Combined With Systemic Chemotherapy and CRS on Peritoneal Metastases From Gastric Cancer

Study Overview
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Brief Summary
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This project is a multi-center, prospective, randomized controlled clinical observation the safety and efficacy that stage IV limited peritoneal metastasis of gastric cancer patients accept hyperthermic intraperitoneal chemotherapy plus neoadjuvant chemotherapy with CRS and systemic chemotherapy. With advanced-stage gastric patients of confined to the peritoneal as the research object, with median progression-free survival and overall survival, adverse events as the end points.

Detailed Description
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Peritoneal metastases in gastric cancer are considered as terminal disease with poor prognosis, the median survival time of this kind of patients is less than 1 year and even worse in China. Recently, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested to improve survival in patients with peritoneal metastases from gastric cancer. 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. Neoadjuvant chemotherapy prolonged OS of patients received macroscopically radical (CC0) surgery. Compared to systemic chemotherapy, HIPEC promotes chemotherapy to penetrate deeper into the cancer tissue, which needed multicenter randomized clinical trials (RCTs) to comfirm. Therefore, we has conducting prospective phase III trial of HIPEC combined with systemic chemotherapy and CRS for gastric cancer with peritoneal metastasis.

Official Title
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A Phase III Study of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Combined With Systemic Chemotherapy And Cytoreductive Surgery (CRS) in the Treatment of Peritoneal Carcinomatosis From Gastric Cancer

Conditions
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Gastric Cancer, Peritoneal Carcinomatosis

Intervention / Treatment
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* Procedure: HIPEC with neoadjuvant chemotherapy
* Procedure: Systemic chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gastic adenocarcinoma is diagnosed by histological and cytological examination. Peritoneal carcinomastosis of gastric cancer is diagnosed by laparotomy or laparoscopic exploration. According to Sugarbaker's peritoneal cancer index (PCI), PCI score of participant is no more than 20. 18 < Age < 70 year old Expected survival > 3 months Performance status: ECOG 0-1 Adequate bone marrow function Hb ≥9 g/dl (After correction in case of iron deficient anemia) WBC ≥ 3,500/mm3, Platelet ≥ 100,000/mm3 Adequate renal function Creatinine ≤ 1.5 mg/dl, and adequate hepatic function Bilirubin ≤ 1.5 mg/dl and AST and ALT ≤ 2.5×ULN 10. Voluntary participation after getting written informed consent. Exclusion Criteria: Except for peritoneal carcinomatosis, gastric cancer concurrently metastasized to liver, lung, para-aortic lymph node and other distant organs. Extensive adhesion in peritoneal cavity Previous History of other malignancies Poorly controlled disease e.g. atrial fibrillation, stenocardia, cardiac insufficiency, persistent hypertension despite medicinal treatment, ejection fraction<50% Receiving other chemotherapy, radiotherapy or immunotherapy Patients who are unsuitable candidates by doctor's decision Without given written informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>HIPEC with paclitaxel 135 mg/m^2+HIPEC with cisplatin 75 mg/m^2±HIPEC with Raltitrexed 3 mg/m^2 intraperitoneally in succession 2 cycles of neoadjuvant chemotherapy: S-1 40-60 mg/m^2, d1-d14, Bid p.o.+ oxaliplatin 130 mg/m^2, d1, IV, every 3 weeks Cytoreductive surgery HIPEC with paclitaxel 135 mg/m^2+HIPEC with cisplatin 75 mg/m^2±HIPEC with Raltitrexed 3 mg/m^2 intraperitoneally in succession 4-6 cycles of adjuvant chemotherapy: S-1 40-60 mg/m^2, d1-d14, Bid p.o.+ oxaliplatin 130 mg/m^2, d1, IV, every 3 weeks | Procedure: HIPEC with neoadjuvant chemotherapy<br>* HIPEC 3 times +NACT 2 cycles +CRS +HIPEC 3 times+ ACT 4-6 cycles<br>* Other names: CRS with HIPEC and adjuvant cheomtherapy;|
| Active Comparator: Control group<br>3 cycles of neoadjuvant chemotherapy: S-1 40-60 mg/m^2, d1-d14, Bid p.o.+ oxaliplatin 130 mg/m^2, d1, IV, every 3 weeks Cytoreductive surgery 4-6 cycles of adjuvant chemotherapy: S-1 40-60 mg/m^2, d1-d14, Bid p.o.+ oxaliplatin 130 mg/m^2, d1, IV, every 3 weeks | Procedure: Systemic chemotherapy<br>* NACT 3 cycles +CRS +ACT 4-6 cycles<br>* Other names: CRS with systemic chemotherpay;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median overall survival | assess median overall survival rate during 3 years in both study arms | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk factors for morbidity and mortality | determine percent of patients wtih Grade I-IV adverse events according to NCI criteria, Common Terminology Criteria for AE (CTCAE 4.0). | Through study completion, an average of 1 year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Cancer, Peritoneal Carcinomatosis, Hyperthermic Intraperitoneal Chemotherapy, Systemic Chemotherapy, Cytoreductive Surgery