Feasibility Study of Intraperitoneal Paclitaxel

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National University Hospital, Singapore
Sponsor:
Information provided by (Responsible Party):
Haematology-Oncology, National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT01739894
First received: October 15, 2012
Last updated: December 8, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Gastric Cancer
Drug: IP Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Feasibility Study of Intraperitoneal Paclitaxel With Oxaliplatin and Capecitabine in Patients With Advanced Gastric Cancer

Resource links provided by NLM:


Further study details as provided by National University Hospital, Singapore:

Primary Outcome Measures:
  • Overall survival (OS) rate [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: 3-weekly ] [ Designated as safety issue: Yes ]
    Toxicity will be monitored 3-weekly and graded according to the National Cancer Institute —Common Terminology Criteria for Adverse Events version 4.0.


Estimated Enrollment: 20
Study Start Date: January 2013
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01739894

Contacts
Contact: Wei Peng Yong, MBBS (65) 6779 5555 Wei_Peng_Yong@nuhs.edu.sg
Contact: Robert Lim, MBBS (65) 6779 5555 Robert_Lim@nuhs.edu.sg

Locations
Singapore
National University Hospital Recruiting
Singapore, Singapore, 119074
Contact: Wei Peng Yong, MBBS    (65) 6779 5555    Wei_Peng_Yong@nuhs.edu.sg   
Contact: Maricel Cordero    (65) 6772 2612    tiemsim_maricel_cordero@nuhs.edu.sg   
Principal Investigator: Wei Peng Yong, MBBS         
Sponsors and Collaborators
National University Hospital, Singapore
Investigators
Principal Investigator: Wei Peng Yong, MBBS National University Hospital, Singapore
  More Information

Additional Information:
Publications:
Responsible Party: Haematology-Oncology, Dr. Yong Wei Peng, National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT01739894     History of Changes
Other Study ID Numbers: GA01/12/12
Study First Received: October 15, 2012
Last Updated: December 8, 2013
Health Authority: Singapore: Domain Specific Review Boards
Singapore: Health Sciences Authority

Keywords provided by National University Hospital, Singapore:
Advanced gastric cancer
unresectable gastric cancer
recurrent gastric cancer
with peritoneal metastasis
cancer cells on peritoneal cytology

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Oxaliplatin
Capecitabine
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 28, 2014