Second Line Chemotherapy for S-1 Refractory Advanced Gastric Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00639327
Recruitment Status : Completed
First Posted : March 20, 2008
Last Update Posted : June 28, 2011
Taiho Pharmaceutical Co., Ltd.
Information provided by:
Japan Clinical Cancer Research Organization

March 5, 2008
March 20, 2008
June 28, 2011
March 2008
April 2011   (Final data collection date for primary outcome measure)
In phase II part, progressive disease rate will be measured for the safety. In phase III part, overall survival will be measured for the benefit of doublet. [ Time Frame: Phase II: 6 weeks from treatment, Phase III: 2 years OS from randomization ]
Same as current
Complete list of historical versions of study NCT00639327 on Archive Site
Adverse events, response rates, progression free survival, time to treatment failure, change over rates to 3rd line [ Time Frame: 2 years ]
Same as current
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Second Line Chemotherapy for S-1 Refractory Advanced Gastric Cancer
Randomized Phase II/III Trial of Second Line Chemotherapy Comparing CPT-11 Monotherapy Versus S-1/CPT-11 Combination for S-1 Refractory Gastric Cancer
The purpose of this study is compare overall survival of the test arm (CPT-11/S-1 combination) to the control arm (CPT-11 alone) in the subjects with S-1 refractory advanced gastric cancer.

Standard chemotherapy for advanced gastric cancer (AGC) in the US is Cisplatin/5-FU (CF) or docetaxel/CF (DCF), is in Europe epirubicin/CF (ECF) or epirubicin/oxaliplatin/ capecitabine (EOX). Until 2006, there was no evidence of standard chemotherapy for AGC in Japan. In 2007, by the results of JCOG9912 trial (5-FU alone vs. CPT-11/CDDP vs S-1) and SPIRITS trial (S-1 alone vs. S-1/CDDP), S-1/CDDP is regarded as a new standard regimen in Japan. In 2008, by the results of TOP-002 trial (s-1 alone vs. S-1/CPT-11), S-1/CPT-11 could not show the superiority to S-1 alone. One of the other phase III trials, JACCRO GC-03 trial (S-1 alone vs. S-1/docetaxel, NCT00287768) is now ongoing. However, the position of CPT-11 in the treatment of AGC will be regarded as a second-line.

In Japan there is a controversy for the treatment of S-1 refractory gastric cancer. The controversy is continuing S-1 (like FOLFOX to FOLFIRI) or not as a second-line. After the successful adjuvant S-1 results (ACTS-GC trial), the same problem will occur in the patients who are recurrent from adjuvant S-1.

Then, we conducted a phase II/III trial of CPT-11 with or without S-1 in the treatment of first-line S-1 refractory AGC.

Phase 2
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Gastric Cancer
  • Drug: S-1 + irinotecan
    Irinotecan 150mg/m2 iv on day one and S-1 po days 1 to 14 every 3 weeks until PD
    Other Names:
    • TS-1
    • CPT-11
  • Drug: irinotecan
    Irinotecan 150mg/m2 iv on day one every two weeks until PD
    Other Name: CPT-11
  • Experimental: A
    CPT-11+ S-1
    Intervention: Drug: S-1 + irinotecan
  • Active Comparator: B
    Intervention: Drug: irinotecan
Tanabe K, Fujii M, Nishikawa K, Kunisaki C, Tsuji A, Matsuhashi N, Takagane A, Ohno T, Kawase T, Kochi M, Yoshida K, Kakeji Y, Ichikawa W, Chin K, Terashima M, Takeuchi M, Nakajima T; JACCRO GC-05 study group. Phase II/III study of second-line chemotherapy comparing irinotecan-alone with S-1 plus irinotecan in advanced gastric cancer refractory to first-line treatment with S-1 (JACCRO GC-05). Ann Oncol. 2015 Sep;26(9):1916-22. doi: 10.1093/annonc/mdv265. Epub 2015 Jun 24.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
June 2011
April 2011   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically proven inoperable advanced gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) or relapse gastric adenocarcinoma
  • Subjects must be able to take orally
  • Subjects must be confirmed to be PD status by picture diagnosis after first-line chemotherapy using S-1 alone, S-1 + Cisplatinum or S-1 + taxane, except S-1 + CPT-11
  • Within 4 weeks from the diagnosis of PD
  • Total dosage of S-1 at the first-line is over 2,240mg/m2 in S-1 alone treatment, 1,680mg/m2 in the S-1 combination
  • ECOG performance status ≤ 1
  • Follow up Age 20 or over
  • Life expectancy estimated more than 12 weeks
  • Hgb ≥ 8 g/dL, WBC 4,000-12,000/mm3, ANC ≥ 2,000/mm3, platelets ≥ 100,000/mm3
  • Creatinine ≤ upper normal limit (UNL)
  • Total bilirubin ≤ 1.5 X UNL
  • Written informed consent

Exclusion Criteria:

  • S-1 + CPT-11 was employed as a first-line
  • Any other cytotoxic agents therapy, immuno-therapy, radiation-therapy
  • After S-1 adjuvant
  • Suspended cases by adverse events by S-1 or S-1 combination
  • Excessive amounts of ascites require drainage
  • Known brain metastases
  • History of hypersensitivity to fluoropyrimidines and CPT-11
  • Pregnancy or lactation women, or women with suspected pregnancy or men with willing to get pregnant
  • Active double cancer
  • Gastrointestinal bleeding
  • Any subject judged by the investigator to be unfit for any reason to participate in the study
Sexes Eligible for Study: All
20 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
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Not Provided
Masashi Fujii/Associate Professor, Department of Digestive Surgery, Surugadai Nihon University Hospital
Japan Clinical Cancer Research Organization
Taiho Pharmaceutical Co., Ltd.
Principal Investigator: Masashi Fujii, M.D.,PhD Surugadai Nihon University Hospital
Japan Clinical Cancer Research Organization
June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP