An Open Label, Multicenter, Randomized, Phase III Study of S-1 and Cisplatin Compared with 5-FU and Cisplatin in patient with metastatic Diffuse Gastric Cancer Previously Untreated with Chemotherapy

Summary

This is an open-label, international, multicenter, two-arm, parallel, randomized,
Phase 3 study evaluating the efficacy and safety of the S-1/cisplatin regimen versus the
5-FU/cisplatin regimen in chemotherapy-naive patients with metastatic diffuse gastric
cancer including carcinoma of the gastro-esophageal junction. Patients will be
screened for eligibility of tumor histology by central review prior to randomization.
Patients will be randomly assigned (2:1) to S-1/cisplatin (experimental arm) or
5-FU/cisplatin (control arm).

Randomization will take place once the consented patient has completed all the
necessary Baseline procedures and is deemed eligible for study entry by the
Investigator and central pathology laboratory. Treatment assignment will be done
centrally using a dynamic allocation method (biased coin) via an Interactive Voice
Response System (IVRS), stratified by:

* Histologic subtype (adenocarcinoma, diffuse type vs signet ring cell
adenocarcinoma),

* Extent of metastasis (1 vs more than 1 metastatic site),

* Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1),

* Region (North America/Western Europe/Eastern Europe/Rest of World [ROW])

Patients will receive study medication until a study treatment discontinuation criterion is met.

Participant Eligibility

A patient must meet all of the following inclusion criteria to be eligible for enrollment in this study:
1. Has given written informed consent.
2. Has histologically confirmed by Central Pathology Review, unresectable (at the time of screening for study eligibility), metastatic diffuse
gastric cancer including carcinoma of the gastro-esophageal junction as defined in Appendix F
(Pathology Central Review: Histologic Criteria). Patients must only be randomized after central
pathology review has confirmed diffuse histologic type. Gastro-esophageal junction involvement
must be documented by endoscopic, radiologic, surgical or pathology report.
3. Has had no prior chemotherapy for gastric cancer; however, adjuvant and/or neo-adjuvant
chemotherapy is permitted if more than 12 months have elapsed between the end of adjuvant or
neo-adjuvant therapy and first recurrence.
4. Has a life expectancy of at least 3 months.
5. Is able to take medications orally and without being crushed or removed from the capsule and given through any form of feeding tube
6. Is >=18 years of age.
7. First dose of study medication will be at least 3 weeks from prior major surgery.
8. First dose of study medication will be at least 4 weeks from prior radiotherapy.
9. Has an ECOG performance status 0 to 1 (see Appendix A).
10. Has adequate organ function as defined by the following criteria:
a. Aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT; SGPT) <=2.5 x
upper limit of normal (ULN); if liver function abnormalities are due to underlying liver
metastasis, AST (SGOT) and ALT (SGPT) <=5 x ULN.
b. Total serum bilirubin of <=1.5 x ULN.
c. Absolute neutrophil count of >=1,500/mm3 (ie, >=1.5 x 109/L by International Units [IU]).
d. Platelet count >=100,000/mm3 (IU: >=100 x 109/L).
e. Hemoglobin value of >=9.0 g/dL based on measurements obtained prior to any transfusions
during the Baseline period.
f. Creatinine clearance (CrCl) >=60 mL/min.
11. Is willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other
study procedures.
12. Women of childbearing potential must have a negative pregnancy test (urine or serum) prior to
randomization. Females and males must agree to adequate birth control if conception is possible during the study males and females must agree to adequate birth control for up to 6 months after
the discontinuation of study medication.