Feasibility Study of Intraperitoneal Paclitaxel

June 6, 2016 updated by: Haematology-Oncology, National University Hospital, Singapore

Feasibility Study of Intraperitoneal Paclitaxel With Oxaliplatin and Capecitabine in Patients With Advanced Gastric Cancer

This is a single arm phase 2 trial evaluating the efficacy and tolerability of intraperitoneal paclitaxel with oxaliplatin and capecitabine in advanced gastric cancer patients with peritoneal metastasis and/or cancer cells on peritoneal cytology. Twenty patients will be recruited into the study for an estimated period of two years. Paclitaxel will be administered intraperitoneally at 40mg/m2 on Day 1 and 8 in patients receiving standard intravenous oxaliplatin 130mg/m2 on Day 1 and capecitabine 1000mg/m2 on day 1-14. The study hypothesizes that the addition of intraperitoneal paclitaxel with chemotherapy will improve treatment efficacy.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The median survival of patients with unresectable gastric cancer treated with systemic chemotherapy is about 12 months. In patients with histologically proven unresectable or recurrent gastric cancer limited to the peritoneum and/or cancer cells in peritoneal cytology, the combination of i.p. paclitaxel with systemic chemotherapy reported a median survival time of 23.6 months. The peritoneal cytology turned negative for 86% of patients. In an updated report, gastrectomy was performed on 52 patients after disappearance or obvious shrinkage of peritoneal metastasis. In this cohort, the median survival time (MST) was 34.9 months. A phase III trial (PHOENIX-GC trial (Phase III study of S-1 plus intravenous and intraperitoneal paclitaxel versus S-1 plus cisplatin for gastric cancer with peritoneal metastasis )) comparing intraperitoneal(IP) regimen with systemic chemotherapy versus systemic therapy alone is currently opened for recruitment in Japan.

The multidisciplinary treatment combining IP-containing chemotherapy and surgery was found to be safe and effective for gastric cancer patients with peritoneal metastasis. A phase I study combining i.p. paclitaxel with oxaliplatin and S-1, found no dose limiting toxicity in all dose levels. Grade 3 neutropenia was observed in one patient at recommended phase 2 dose (RP2D) of i.p. paclitaxel of 40 mg/m2. In addition, grade 2 non-hematological toxicities observed were anorexia (n=6/12), fatigue (n=4/12) and nausea (n=2/12).

Both S-1 and capecitabine are orally available fluoropyrimidine. When combined with oxaliplatin, both S-1 and capecitabine were found to be equally active and well tolerated in advanced gastric cancer patients. As S-1 is not yet widely available worldwide, the combination of capecitabine and a platinum chemotherapy is still one of the most commonly adopted chemotherapy regimen for patients with advanced gastric cancer. In this study, we intend to assess the efficacy and feasibility of combining weekly i.p. paclitaxel with oxaliplatin and capecitabine.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically proven unresectable or recurrent adenocarcinoma of stomach and gastroesophageal junction
  • Patients without prior systemic treatment. Patients who completed postoperative adjuvant chemotherapy (and radiotherapy) more than 180 days before may be enrolled
  • Peritoneal metastasis and/or cancer cells on peritoneal cytology
  • Age >21 years
  • Eastern Cooperative Oncology Group performance status 0-2
  • Adequate bone marrow function (neutrophil count >1500/mm3, hemoglobin >8.0 g/dl and platelet count >100 000/mm3)
  • Adequate liver function (bilirubin, AST (aspartate aminotransferase)/ALT (alanine aminotransferase) within upper limit of normal)
  • Adequate renal function (serum creatinine within the upper limit of normal)
  • Expected survival >3 months
  • Able to take orally
  • Able to understand and the willingness to sign a written informed consent document
  • The effects of proposed regimen on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because antitumor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

  • Metastasis to distant organ sites (such as the liver, lungs or bone)
  • When trastuzumab is considered for palliative chemotherapy
  • Known allergy to taxane, fluoropyrimidine or oxaliplatin
  • Previous malignancy other than gastric cancer diagnosed in the last 5 years except for basal cell carcinoma of skin or preinvasive cancer of cervix
  • Patients with reproductive potential who refuse to use an adequate means of contraception (including male patients)
  • Significant disease or conditions which, in the investigator's opinion, would exclude patient from the study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or lactating female

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IP Paclitaxel
Paclitaxel will be administered intraperitoneally at 40mg/m2 on Days 1 and 8 in a 21-day cycle in patients receiving intravenous oxaliplatin 100mg/m2 on Day 1 and capecitabine 1000mg/m2 twice daily on Days 1-14.
Drug: IP Paclitaxel
Each treatment cycle will consist of 21 days, with 14 days on treatment and 7 days off-treatment. Oxaliplatin will be administered intravenously (on Day 1 of each cycle). Paclitaxel will be administered intra-abdominally on Day 1 and Day 8 of each cycle. In particular, a needle will be inserted into the intraperitoneal injection port for normal saline to be injected intra-abdominally over one hour, followed by paclitaxel chemotherapy over a further one hour. Capecitabine will be taken by mouth from Day 1 to 14 of each cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS) rate
Time Frame: 1 year
The primary end point is 1-year survival because most patients may not have measurable disease, hence response rate and progression free survival are less easy to assess.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with adverse events
Time Frame: 3-weekly
Toxicity will be monitored 3-weekly and graded according to the National Cancer Institute -Common Terminology Criteria for Adverse Events version 4.0.
3-weekly

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National University Hospital, Singapore

Investigators

  • Principal Investigator: Wei Peng Yong, MBBS, National University Hospital, Singapore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Anticipated)

November 1, 2017

Study Completion (Anticipated)

August 1, 2018

Study Registration Dates

First Submitted

October 15, 2012

First Submitted That Met QC Criteria

November 28, 2012

First Posted (Estimate)

December 4, 2012

Study Record Updates

Last Update Posted (Estimate)

June 7, 2016

Last Update Submitted That Met QC Criteria

June 6, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GA01/12/12

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe