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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2009 by National Cancer Center, Korea.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Seoul National University Bundang Hospital
Chungbuk National University
Gachon University Gil Medical Center
Information provided by:
National Cancer Center, Korea
ClinicalTrials.gov Identifier:
NCT00980603
First received: September 18, 2009
Last updated: NA
Last verified: September 2009
History: No changes posted
  Purpose

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


Condition Intervention Phase
Gastric Cancer
Drug: docetaxel
Drug: docetaxel, cisplatin
Drug: docetaxel, S-1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Center, Korea:

Primary Outcome Measures:
  • response rate [ Time Frame: every 2 cycles ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • time to progression [ Time Frame: every 2 cycles ] [ Designated as safety issue: No ]

Estimated Enrollment: 144
Study Start Date: November 2008
Estimated Study Completion Date: May 2011
Estimated Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00980603

Contacts
Contact: Sook Ryun Park, Dr. 82-31-920-1609 ext 1609 sukryun73@hanmail.net
Contact: Young Lan Park, CRC 82-31-920-0422 ext 0422 lan0729@hanmail.net

Locations
Korea, Republic of
Chungbuk National University Hospital Recruiting
Chonju, Korea, Republic of, 361-711
Contact: Hye-Suk Han, M.D.       sook3529@hanmail.net   
Sub-Investigator: Hye-Suk Han, M.D.         
Research Institute and Hospital, National Cancer Center Korea Recruiting
Goyang, Korea, Republic of, 410-769
Contact: Sook Ryun Park, M.D.    82-31-920-1609 ext 1609    sukryun73@hanmail.net   
Contact: Young Lan Park, RN    82-31-920-0422 ext 0422    lan0729@hanmail.net   
Principal Investigator: Sook Ryun Park, M.D.         
Sub-Investigator: Noe Kyeong Kim, M.D., Ph.D.         
Sub-Investigator: Youngiee Park, M.D., Ph.D.         
Sub-Investigator: Byung-Ho Nam, Ph.D.         
Gachon University Gil Hospital Not yet recruiting
Inchon, Korea, Republic of, 405-760
Contact: Dong Bok Shin, M.D., Ph.D.       dbs@gilhospital.com   
Principal Investigator: Dong Bok Shin, M.D., Ph.D.         
Sub-Investigator: Sun Jin Sym, M.D.         
Seoul National University Bundang Hospital Recruiting
Seongnam, Korea, Republic of, 463-707
Contact: Keun-Wook Lee, M.D., Ph.D.       hmodoctor@hanmail.net   
Principal Investigator: Keun-Wook Lee, M.D., Ph.D.         
Sponsors and Collaborators
National Cancer Center, Korea
Seoul National University Bundang Hospital
Chungbuk National University
Gachon University Gil Medical Center
Investigators
Principal Investigator: Sook Ryun Park, Dr. Research Institute and Hospital, National Cancer Center Korea
  More Information

No publications provided

Responsible Party: Sook Ryun Park/Dr., Research Institute and Hospital, National Cancer Center
ClinicalTrials.gov Identifier: NCT00980603     History of Changes
Other Study ID Numbers: NCCCTS-07-296
Study First Received: September 18, 2009
Last Updated: September 18, 2009
Health Authority: Korea: Food and Drug Administration

Keywords provided by National Cancer Center, Korea:
gastric cancer
metastatic
docetaxel
cisplatin
S-1

Additional relevant MeSH terms:
Stomach Diseases
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Docetaxel
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014