Intraperitoneal Docetaxel With Cisplatin and TS-ONE for Gastric Cancer With Peritoneal Carcinomatosis

May 1, 2018 updated by: Dr. Lam Ka On, The University of Hong Kong

Feasibility Study of Intraperitoneal Docetaxel Combined With Intravenous Cisplatin and Oral TS-ONE for Gastric Cancer Patients With Peritoneal Carcinomatosis

Phase I study on the maximum tolerated dose (MTD) and the recommended dose (RD) of intraperitoneal docetaxel combined with intravenous cisplatin and oral TS-ONE in gastric cancer patients with peritoneal carcinomatosis

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Peritoneal carcinomatosis (PC) is common in advanced gastric cancer, and it carries a poor prognosis; the median survival time is 3 to 6 months. Gastric cancer with PC is considered incurable and patients are subjected to non-surgical treatment, mainly chemotherapy. Currently, there is no established standard treatment for these patients.

Multidisciplinary approach to the treatment of gastric cancer including chemotherapy, radiotherapy and surgery has been developed and survival benefit has been demonstrated in the adjuvant setting. Novel chemotherapeutic agents: taxanes (paclitaxel and docetaxel), irinotecan, oxaliplatin, fluoropyrimidine (TS-ONE and capecitabine) have shown activity in gastric cancer. Various combination chemotherapy regimens for unresectable and metastatic gastric cancer are practised in different parts of the world. Epirubicin, cisplatin and 5-fluorouracil (ECF) are used in Europe, while TS-ONE and cisplatin are commonly used in Asian countries such as Japan and Korea. The median survival time (MST) with these regimens was 8.9 and 13 months, respectively. Use of docetaxel, cisplatin and 5-fluorouracil (DCF) was proposed in the V325 study, MST was 9.2 months but the toxicity (grade 3-4 neutropenia) was reported to be significantly higher in DCF group when compared with CF group. However, there are few trials to study the specific efficacy of these regimens on PC.

Systemic chemotherapy is considered to be less effective against PC due to the existence of the blood-peritoneal barrier (BPB). The barrier inhibits the movement of drugs from systemic circulation to the peritoneal cavity. Intraperitoneal (IP) chemotherapy has the advantage of maintaining a high drug concentration in the peritoneal cavity, and reduces the systemic toxicity. Paclitaxel and docetaxel have been shown to have high peritoneal concentration in animal studies and are considered ideal drugs for IP administration.

Neoadjuvant intraperitoneal/systemic chemotherapy (NIPS) is a new bidirectional induction chemotherapy for treatment of PC from gastric cancer. The aim of NIPS is to induce a reduction of PC volume. Bidirectional means that NIPS could attack PC from both the peritoneal cavity and the subperitoneal blood vessels. Patients with good response to NIPS may undergo subsequent gastrectomy. The use of TS-ONE and IP taxane (paclitaxel/docetaxel) had been studied in phase I and II trials. Ischigami et al. reported 1-year survival rate of 78% and overall response rate of 56% using weekly intravenous and IP paclitaxel combined with TS-ONE. Fujiwara et al. reported 78% patients had negative peritoneal cytology after NIPS and 16 out of 18 patients (88.9%) underwent subsequent gastrectomy, with a MST of 24.6 months. No treatment-related mortality has been reported.

Systemic DCF is associated with significant toxicity, yet it is superior to CF alone in terms of survival (9.2 months vs. 8.6 months, p<0.02). Grade III/IV neutropenia was reported to be 82%. It is postulated that switching from intravenous docetaxel to IP docetaxel may improve its efficacy against PC and reduce the systemic toxicity. TS-ONE contains tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo). Dihydropyrimidine dehydrogenase (DPD), which is found in liver, rapidly degrades 5-FU. The presence of CDHP, a specific inhibitor of DPD, allows a high intraperitoneal drug concentration after oral administration of TS-ONE that has been demonstrated in an experimental model.

Therefore we propose a modification of the DCF regimen using IP docetaxel, intravenous cisplatin and oral TS-ONE in the treatment of gastric cancer patients with PC. We aim to study the maximum tolerated dose (MTD) and the recommended dose (RD) of IP docetaxel while using fixed doses of cisplatin and TS-ONE. Data on treatment efficacy will also be recorded. By far there is no study on IP chemotherapy in Hong Kong.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

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

  • China
    • Hong Kong
      • Hong Kong, Hong Kong, China
        • The University of Hong Kong

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

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age≥18
  • Histologic confirmation of gastric adenocarcinoma
  • Positive peritoneal cytology or histological proven PC
  • Absence of other distant metastases except peritoneum and lymph node(s)
  • Adequate bone marrow and organ functions as defined below:
  • Leucocyte ≥3.00 x 109/L
  • Absolute neutrophil counts ≥ 1.50 x 109/L
  • Platelet ≥ 100 x 109/L
  • Total bilirubin ≤2 x ULN
  • AST/ALT ≤2.5 x ULN
  • Creatinine clearance ≥60ml/min
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Subjects of child-bearing potential must agree to contraception from screening to 6 months after completion of treatment
  • Provision of written informed consent

Exclusion Criteria:

  • Any prior anti-cancer therapy for gastric cancer
  • Previous exposure to taxane, fluoropyrimidine or platinum chemotherapy
  • Previous radiotherapy to abdomen or pelvic region
  • Known hypersensitivity to study medication
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency
  • Any prior or synchronous malignancy, except,
  • Malignancy treated with curative intent and with no evidence of disease for ≥5 years prior to enrollment and considered to be at low risk for recurrence by the treating physician
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Subject is pregnant or breast feeding
  • Any serious concomitant illness

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Intraperitoneal docetaxel

Intraperitoneal docetaxel in 1litre normal saline infused over 1 hour on day 1 every 3 weeks:

- Level I: 40mg/m2; Level II: 50mg/m2; Level III: 60mg/m2

Intravenous cisplatin: 60mg/m2 on day 1 every 3 weeks

Oral TS-ONE: 40-60mg twice daily on day 1 -14 every 3 weeks
Drug: Intraperitoneal docetaxel
Intraperitoneal docetaxel, intravenous cisplatin and oral TS-ONE every 3 weeks for 3 cycles then stop
Other Names:
  • Intraperitoneal taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose and recommended dose
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 3 years
3 years
Clinical response rate
Time Frame: 12 weeks
12 weeks

Collaborators and Investigators

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

Sponsor

The University of Hong Kong

Collaborators

Taiho Pharmaceutical Co., Ltd.

Investigators

  • Principal Investigator: Ka-On Lam, MBBS, The University of Hong Kong

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 (ACTUAL)

December 1, 2013

Primary Completion (ACTUAL)

February 1, 2017

Study Completion (ACTUAL)

March 1, 2018

Study Registration Dates

First Submitted

December 27, 2013

First Submitted That Met QC Criteria

December 27, 2013

First Posted (ESTIMATE)

December 31, 2013

Study Record Updates

Last Update Posted (ACTUAL)

May 4, 2018

Last Update Submitted That Met QC Criteria

May 1, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HKUGCDTC01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

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