Phase III Study of Docetaxel + S-1 vs. S-1 for Advanced Gastric Cancer

• ClinicalTrials.gov Identifier: NCT00287768
• Recruitment Status: Completed
• First Posted: February 7, 2006
• Last Update Posted: June 28, 2011
• Sponsor: Japan Clinical Cancer Research Organization
• Collaborator: Korean Cancer Study Group
• Information provided by: Japan Clinical Cancer Research Organization

Tracking Information

• First Submitted Date: February 3, 2006
• First Posted Date: February 7, 2006
• Last Update Posted Date: June 28, 2011
• Study Start Date: March 2006
• Actual Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 2, 2007): overall survival [ Time Frame: median ]
• Original Primary Outcome Measures (submitted: February 3, 2006): Median overall survival

Current Secondary Outcome Measures (submitted: August 2, 2007)

• time-to-progression [ Time Frame: From onset of regression to progression ]
• response rate [ Time Frame: response during observation ]
• safety [ Time Frame: side effects during observation ]

Original Secondary Outcome Measures (submitted: February 3, 2006)

• time-to-tumor progression
• clinical response
• safety

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase III Study of Docetaxel + S-1 vs. S-1 for Advanced Gastric Cancer
• Official Title: A Phase III Study of Docetaxel and S-1 Versus S-1 in the Treatment of Advanced Gastric Cancer
• Brief Summary: The primary objective of this study is to compare median overall survival of the test arm (docetaxel and S-1) to the control arm (S-1 only) in subjects with advanced or recurrent gastric cancer.

Detailed Description

Seven-hundred and fifty thousand of new gastric cancer cases are diagnosed worldwide per year. Advanced gastric cancer (AGC) is considered nearly incurable with less than 10% of subjects alive 5 years after diagnosis. Therefore, new treatment regimens are needed for subjects with AGC.

S-1, a new oral fluoropyrimidine which consists of the 5-FU prodrug tegafur (ftorafur, FT) and two enzyme inhibitors, CDHP (5-chloro-2,4-dihydroxypyridine) and OXO (potassium oxonate), in a molar ratio of 1(FT):0.4 (CDHP):1(OXO) is commercially available since late 90'in Japan. Phase II trials have demonstrated that S-1 is active, as a single agent, for the treatment of gastric (RR 44.6%), colorectal (RR 37.4%), head and neck, breast, non-small cell lung, and pancreatic cancers. In gastric cancer, phase III trials (JCOG 9912) comparing 5-FU alone and CPT-11/CDDP combination are currently underway and these results are awaited. Despite of JCOG 9912 study is ongoing, 80% of patients of AGC are already treated by S-1, because of high RR and convenience use for out-patient basis. P-II studies S-1/CDDP, S-1/CPT-11 and S-1/Docetaxel showed high RR(55-76%) and long MST(12-14M). Furthermore, P-III studies are already conducted S-1 vs. S-1/CDDP and S-1 vs. S-1/CPT-11 in Japan. The aim of this study is to compare S-1/Docetaxel vs. S-1 alone in the patients of AGC. This study is a prospective, multicenter, multinational, non-blinded, randomized phase III study.

Patients: Inoperable or relapse gastric cancer. Informed consent must be obtained in writing before treatment. Subjects meeting all of the inclusion criteria and exclusion criteria will be considered for enrollment into study. Then patients will be randomly assigned into two groups S-1/Docetaxel(Treatment Arm A) or S-1 alone(Treatment Arm B).

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Gastric Cancer

Intervention

• Drug: docetaxel + S-1
  Docetaxel iv on day one and S-1 po days 1 to 14 every 3 weeks
  Other Names:

  • taxotere
  • TS-1
• Drug: S-1
  S-1 po days 1-28 every 6 weeks
  Other Name: TS-1

Study Arms

• Experimental: 1
  Docetaxel + S-1
  Intervention: Drug: docetaxel + S-1
• Active Comparator: 2
  S-1
  Intervention: Drug: S-1

Publications *

• Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T; JACCRO and KCSG Study Group. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol. 2014 Feb;140(2):319-28. doi: 10.1007/s00432-013-1563-5. Epub 2013 Dec 24.
• Fujii M; 0. Chemotherapy for advanced gastric cancer: ongoing phase III study of S-1 alone versus S-1 and docetaxel combination (JACCRO GC03 study). Int J Clin Oncol. 2008 Jun;13(3):201-5. doi: 10.1007/s10147-008-0775-1. Epub 2008 Jun 14.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: February 3, 2006): 628
• Original Enrollment: Same as current
• Actual Study Completion Date: October 2010
• Actual Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically proven in operable advanced gastric adenocarcinoma (including adenocarcinoma of the gastrooesophageal junction) or relapse gastric adenocarcinoma
• Subjects must be able to take orally
• Measurable lesion and/or non-measurable lesion defined by RECIST
• ECOG performance status ≦ 1
• Hgb ≧ 8g/dL, WBC 4000-12000/mm3, platelets ≧ 100,000/mm3
• Creatine ≦ upper normal limit (UNL)
• Total bilirubin ≦ 1.5 X UNL
• AST, ALT and ALP ≦ 2.5 x UNL
• No prior chemotherapy
• Life expectancy estimated than 3 months
• Written informed consent

Exclusion Criteria:

• Active double cancer
• Gastrointestinal bleeding
• Excessive amounts of ascites require drainage
• Known brain metastases
• Symptomatic peripheral neuropathy ≧ garde 2. by NCI-CTCAE ver.3.0
• Pulmonary fibrosis, Intestinal pneumonitis
• History of hypersensitivity to fluoropyrimidines, docetaxel or medications formulated with polysorbate 80
• Any previous chemotherapy or radiotherapy for AGC
• Pregnancy or lactation women, or women with suspected pregnancy or men with willing to get pregnant
• Treatment with any investigational product during the last 4 weeks prior to study entry
• Definite contraindications for the use of corticosteroids
• Any subject judged by the investigator to be unfit for any reason to participate in the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 79 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT00287768
• Other Study ID Numbers: JACCRO GC-03
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Masashi Fujii / Associate Professor, Department of Surgery, Surugadai Nippon University
• Original Responsible Party: Not Provided
• Current Study Sponsor: Japan Clinical Cancer Research Organization
• Original Study Sponsor: Same as current
• Collaborators: Korean Cancer Study Group

Investigators

• Principal Investigator: Masashi Fujii, MD PhD; Surugadai Nihon University Hospital

• PRS Account: Japan Clinical Cancer Research Organization
• Verification Date: June 2011