The Study of Intraperitoneal Docetaxel Plus S-1 for Malignant Ascites

Study Overview
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Brief Summary
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This is a clinical Study to evaluate the effect, survival benefit and safety of intraperitoneal docetaxel combined with oral S-1 for advanced gastric cancer with malignant ascites.

Detailed Description
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Peritoneal metastasis(PM) is common in advanced gastric cancer and associated with a poor prognosis. The median survival time is 3 to 4 months and even shorter in the patients with malignant ascites. Systemic chemotherapy is considered to be less effective against peritoneal metastasis (PM) due to the existence of the blood-peritoneal barrier (BPB), which inhibits the movement of drugs from systemic circulation to the peritoneal cavity. S-1 is one kind of oral fluoropyrimidine derivatives and has been reported to be effective on PM. Docetaxel (DTX) has a pharmacokinetic advantage after intraperitoneal（IP）delivery which is hundreds of times higher than systemic administration. The use of S-1 and docetaxel has been studied in some phase II trials. Fujiwara and Fushida reported the usefulness of IP docetaxel combined with oral S-1 regimen in gastric cancer with PM respectively，the median survival time can exceed 16 months and one year survival rate was over 70%. Therefore, the investigators suppose IP docetaxel and oral S-1 can also be effective for gastric cancer with malignant ascites and start this study. This is a single center, open-label, prospective clinical trial. Patients with histological proven gastric cancer with ascites, who fulfill the inclusion and exclusion criteria, can be recruited in this study. Patients will be firstly received laparoscopic exploration for Peritoneal Cancer Index (PCI）score, extraction of 100ml ascites for cytology examination, and one peritoneal access port is implanted in the subcutaneous space of the lower abdomen. Then patients were treated with chemotherapy on the first day after operation, the regimen as follows: DTX is administered IP at a dose of 60 mg/m2 on day 1. DTX is diluted in 1 litre normal saline and administered through the implanted peritoneal access port over 1 hour. S-1 was administered orally twice daily at a dose of 80 mg/m2 per day for 14 consecutive days, followed by 7 days of rest. The treatment course will be repeated every three weeks until observation of disease progression or unacceptable toxicity. Before each intraperitoneal chemotherapy, investigators extract 50-100 ml ascites for cytology pathologic examination, the abdominal CT will be reviewed after every three course to evaluate the volume of ascites. The volume of ascites before and after therapy, PCI scores, ascites cytology results, complications, side effects and conditions of survival state and follow-up will be recorded and analyzed to evaluate the effect, survival benefit and safety of this study.

Official Title
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The Study of Intraperitoneal Docetaxel Plus S-1 for Malignant Ascites Due to Far Advanced Gastric Cancer

Conditions
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Stomach Neoplasms, Peritoneal Metastasis

Intervention / Treatment
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* Drug: intraperitoneal docetaxel
* Drug: oral S-1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 20-75years Histologic confirmation of gastric adenocarcinoma Positive peritoneal cytology or histological proven PM Ascites in CT scan Performance status (PS) ≤ 2 on Eastern Cooperative Oncology Group (ECOG) scale Adequate bone marrow and organ functions as defined below: Leucocyte≥3,000/ul Absolute neutrophil counts ≥1,500/uL Platelet≥100,000/uL Total bilirubin≤1.5mg/dl ALT，AST≤ 2x ULN serum creatinine ≤1.5mg/dl Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Provision of written informed consent Exclusion Criteria: Presence of non-curable factors such as distant metastasis to liver or lung except of peritoneum Other severe medical conditions such as symptomatic infectious disease,active hemorrhage/bleeding, or obstructive bowel disease Life expectation ≤ 3 months With other malignant tumor allergy to therapeutic drugs

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: intraperitoneal docetaxel and oral S-1<br>Docetaxel is diluted in 1litre normal saline and administered intraperitoneal（IP）at a dose of 60 mg/m2 over 1 hour on day 1. S-1 was administered orally twice daily at a dose of 40mg/m2 per day for 14 consecutive days, followed by 7 days of rest. Intervention: Drug: Intraperitoneal docetaxel Intervention：Drug：Oral S-1 | Drug: intraperitoneal docetaxel<br>* One peritoneal access port will be implanted in subcutaneous space of patients' abdominal wall after laparoscopic exploration.Then intraperitoneal docetaxel in 1litre normal saline will be administered through the port<br>* Other names: intraperitoneal chemotherapy;Drug: oral S-1<br>* 40mg/m² twice daily on day 1-14 every 3 weeks<br>* Other names: systemic chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate of ascites | From date of enrollment to three cycles of treatment，the ascites is evaluated by the Japanese conventional five-point method | 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| one year survival rate | From date of enrollment until 1 year | 1 year | 
| side effects of chemotherapy | Grade refers to Common Terminology Criteria for Adverse Events（CTCAE）Version4.0 | 1 week to 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malignant ascites