Docetaxel Versus Docetaxel Plus Cisplatin Versus Docetaxel Plus S-1 as Second-line Chemotherapy in Metastatic Gastric Cancer

September 18, 2009 updated by: National Cancer Center, Korea

A Randomized Phase II Study of Docetaxel vs. Docetaxel Plus Cisplatin vs. Docetaxel Plus S-1 as Second-line Chemotherapy After Cisplatin Plus S-1 or Capecitabine in Metastatic Gastric Cancer

The purpose of this study is to assess efficacy and safety of docetaxel alone, docetaxel plus cisplatin, and docetaxel plus S-1 in patients with metastatic gastric cancer after failing 1st line chemotherapy with cisplatin plus S-1 or capecitabine

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

To date, the most commonly used first-line chemotherapies have been based on fluorouracil and/or cisplatin in patients with metastatic gastric cancer. Unfortunately, considerable proportions of patients with metastatic gastric cancer do not respond to first-line chemotherapy and most of the patients who do respond eventually experience disease progression. In the second-line treatment, however, standard therapies are less clearly defined.

Meanwhile, regarding re-challenge of previous failed drugs as a combination with an other newly introduced chemotherapeutic agent, there are few data. Increased expression and activity of thymidylate synthase, which is inhibited by fluoropyrimidine, is regarded to be the main reason for the development of clinical resistance to fluoropyrimidine. Since the cotreatment of docetaxel and 5-fluorouracil decreases the activity and expression of thymidylate synthase and dihydropyrimidine dehydrogenase (5-fluorouracil degradation enzyme), and increases the expression of orotate phosphoribosyl transferase, the addition of docetaxel into S-1 may recover the sensitivity to S-1 in patients previously resistant to S-1.

Several reports found that MDR-1 and MRP-1 are related to cisplatin-resistance; cisplatin induces the overexpression of MRP-1, which reduces intracellular cisplatin accumulation. Since docetaxel suppresses the cisplatin-induced MRP-1 upregulation, the addition of docetaxel into cisplatin may recover the sensitivity to cisplatin in patients previously resistant to cisplatin.

Based on these synergism mechanisms, we speculate that the cotreatment of docetaxel and cisplatin or S-1 has better anti-tumor activity than docetaxel alone in patients resistant to cisplatin or S-1.

Study Type

Interventional

Enrollment (Anticipated)

144

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 Contact

Study Contact Backup

Study Locations

  • Korea, Republic of
      • Chonju, Korea, Republic of, 361-711
        • Recruiting
        • Chungbuk National University Hospital
        • Contact:
        • Sub-Investigator:
          • Hye-Suk Han, M.D.
      • Goyang, Korea, Republic of, 410-769
        • Recruiting
        • Research Institute and Hospital, National Cancer Center Korea
        • Contact:
        • Contact:
        • Principal Investigator:
          • Sook Ryun Park, M.D.
        • Sub-Investigator:
          • Noe Kyeong Kim, M.D., Ph.D.
        • Sub-Investigator:
          • Youngiee Park, M.D., Ph.D.
      • Inchon, Korea, Republic of, 405-760
        • Not yet recruiting
        • Gachon University Gil Hospital
        • Contact:
        • Principal Investigator:
          • Dong Bok Shin, M.D., Ph.D.
        • Sub-Investigator:
          • Sun Jin Sym, M.D.
      • Seongnam, Korea, Republic of, 463-707
        • Recruiting
        • Seoul National University Bundang Hospital
        • Contact:
        • Principal Investigator:
          • Keun-Wook Lee, M.D., Ph.D.

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:

  • Histologically or cytologically confirmed gastric adenocarcinoma with metastatic disease
  • Age ≥18 years
  • Eastern Cooperative Oncology Group performance status 0-2
  • At least one measurable lesion as defined by RECIST
  • Only one prior chemotherapy containing both S-1 or capecitabine and cisplatin for metastatic gastric cancer with documented progression of disease occurring during chemotherapy or within 6 months of completion of chemotherapy
  • Adequate major organ function:

ANC ≥1,500/mm3, Platelet ≥100,000/mm3, serum bilirubin ≤1.5 x upper limit of normal (ULN), AST/ALT ≤2.5 x ULN (≤5 x ULN if liver metastases are present), creatinine clearance ≥50 ml/min using the calculation formula or 24 hours urine collection

  • Patients should sign a written informed consent before study entry

Exclusion Criteria:

  • Prior taxane treatment
  • Major surgery or radiotherapy less than 4 weeks prior to entry
  • NCI CTCAE (version 3.0) adverse events ≥grade 2 except alopecia, fatigue, and weight loss
  • Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome, or inability to take oral medication
  • Patients with active gastrointestinal bleeding
  • Inadequate cardiovascular function
  • Serious concurrent infection or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy
  • Other malignancy within the past 3 years except adequately treated non-melanomatous skin cancer, carcinoma in situ of the cervix, or in situ of prostate cancer Gleason≤7
  • Psychiatric disorder that would preclude compliance
  • Patients receiving a concomitant treatment with drugs interacting with S-1 such as flucytosine, phenytoin, or allopurinol
  • Female patients who are pregnant or breast feeding or adults of reproductive potential not employing effective method of birth control

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: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: docetaxel
Drug: docetaxel
docetaxel 75 mg/m2, IV on day 1 of each 3 week cycle until progression or unacceptable toxicity develops
EXPERIMENTAL: doctaxel plus cisplatin
Drug: docetaxel, cisplatin
docetaxel 60 mg/m2 and cisplatin 60 mg/m2, IV on day 1 of each 3 week cycle until progression or unacceptable toxicity develops
EXPERIMENTAL: docetaxel plus S-1
Drug: docetaxel, S-1
docetaxel 60 mg/m2 IV on day 1 and S-1 30 mg/m2 bid PO on days 1-14 of each 3 week cycle until progression or unacceptable toxicity develops

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
response rate
Time Frame: every 2 cycles
every 2 cycles

Secondary Outcome Measures

Outcome Measure
Time Frame
time to progression
Time Frame: every 2 cycles
every 2 cycles

Collaborators and Investigators

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

Sponsor

National Cancer Center, Korea

Collaborators

Seoul National University Bundang Hospital
Gachon University Gil Medical Center
Chungbuk National University Hospital

Investigators

  • Principal Investigator: Sook Ryun Park, Dr., Research Institute and Hospital, National Cancer Center Korea

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

November 1, 2008

Primary Completion (ANTICIPATED)

November 1, 2010

Study Completion (ANTICIPATED)

May 1, 2011

Study Registration Dates

First Submitted

September 18, 2009

First Submitted That Met QC Criteria

September 18, 2009

First Posted (ESTIMATE)

September 21, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

September 21, 2009

Last Update Submitted That Met QC Criteria

September 18, 2009

Last Verified

September 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCCCTS-07-296

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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