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

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

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.

Study Overview

• Status: Unknown
• Conditions: Stomach Neoplasms; Peritoneal Metastasis
• Intervention / Treatment: Drug: intraperitoneal docetaxel; Drug: oral S-1

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Recruiting
      • Huashan Hospital
      • Contact: jun wang, Doctor; Phone Number: 13611697522; Email: wangjun01cn@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 20-75years
2. Histologic confirmation of gastric adenocarcinoma
3. Positive peritoneal cytology or histological proven PM
4. Ascites in CT scan
5. Performance status (PS) ≤ 2 on Eastern Cooperative Oncology Group (ECOG) scale

6. 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

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
8. Provision of written informed consent

Exclusion Criteria:

1. Presence of non-curable factors such as distant metastasis to liver or lung except of peritoneum
2. Other severe medical conditions such as symptomatic infectious disease,active hemorrhage/bleeding, or obstructive bowel disease
3. Life expectation ≤ 3 months
4. With other malignant tumor
5. allergy to therapeutic drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intraperitoneal docetaxel and oral S-1; 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; 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; Other Names: intraperitoneal chemotherapy; Drug: oral S-1; 40mg/m² twice daily on day 1-14 every 3 weeks; Other Names: systemic chemotherapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2017
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: May 15, 2016
• First Submitted That Met QC Criteria: May 19, 2016
• First Posted (Estimate): May 20, 2016

Study Record Updates

• Last Update Posted (Estimate): January 24, 2017
• Last Update Submitted That Met QC Criteria: January 23, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: malignant ascites
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Ascites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: Ifen

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No