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

Study Overview
=================
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).

Official Title
-----------------
A Phase III Study of Docetaxel and S-1 Versus S-1 in the Treatment of Advanced Gastric Cancer

Conditions
-----------------
Gastric Cancer

Intervention / Treatment
-----------------
* Drug: docetaxel + S-1
* Drug: S-1


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Docetaxel + S-1 | Drug: docetaxel + S-1<br>* Docetaxel iv on day one and S-1 po days 1 to 14 every 3 weeks<br>* Other names: TS-1;|
| Active Comparator: 2<br>S-1 | Drug: S-1<br>* S-1 po days 1-28 every 6 weeks<br>* Other names: TS-1;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | median | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time-to-progression |  | From onset of regression to progression | 
| response rate |  | response during observation | 
| safety |  | side effects during observation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
gastric cancer, advanced gastric cancer, S-1, docetaxel, phase III study