Diffuse Gastric and Esophagogastric Junction Cancer S-1 Trial (DIGEST)

• Progression-free survival (PFS) [ Time Frame: Throughout ] [ Designated as safety issue: No ]
• Time to treatment failure (TTF) [ Time Frame: Throughout ] [ Designated as safety issue: No ]
• Antitumor activity: Overall Response Rate (ORR), duration of response (DR), time to tumor response (TTR); [ Time Frame: Throughout ] [ Designated as safety issue: No ]
• Safety and tolerability [ Time Frame: Treatment period ] [ Designated as safety issue: Yes ]

The purpose of this study is to evaluate the safety and efficacy of S-1 and Cisplatin compared to 5-FU and Cisplatin in treatment of patients with metastatic diffuse gastric and esophagogastric junction cancer previously untreated with chemotherapy.

This is an open-label, international, Phase 3 study evaluating the efficacy and safety of the S-1/cisplatin regimen versus the 5-FU/cisplatin regimen in chemotherapy-naïve patients with metastatic diffuse gastric carcinoma including carcinoma of the gastro-esophageal junction. Patients will be randomly assigned to S-1/cisplatin (experimental regimen, Arm A) or 5-FU/cisplatin (control regimen, Arm B).

• Drug: S-1 (Tegafur/Gimeracil/Oteracil) /cisplatin (investigational arm)
  25 mg/m² body surface area (BSA) orally 2 times daily from Days 1 through 21 followed by a 7 day rest period, plus cisplatin 75 mg/m2 BSA on Day 1 each 28 day cycle Number of Cycles: until progression or unacceptable toxicity develops. Treatment with cisplatin is limited to a maximum of 8 cycles.
  Other Name: TS-1, Tegafur/Gimeracil/Oteracil
• Drug: Fluorouracil/cisplatin (control arm)

  5-FU: 800 mg/m2 BSA/24 hours by continuous intravenous infusion (CIV) from Days 1 through 5 plus cisplatin 80 mg/m2 BSA on Day 1 each 21 day cycle.

  Number of Cycles: until progression or unacceptable toxicity develops. Treatment with cisplatin is limited to a maximum of 8 cycles.

  Other Name: TS-1, Tegafur/Gimeracil/Oteracil

• Experimental: S-1/cisplatin
  Intervention: Drug: S-1 (Tegafur/Gimeracil/Oteracil) /cisplatin (investigational arm)
• Active Comparator: 5-FU/cisplatin
  Intervention: Drug: Fluorouracil/cisplatin (control arm)

Inclusion Criteria:

• Has given written Informed Consent
• Histologically confirmed, unresectable, metastatic diffuse gastric cancer including carcinoma of the gastro-esophageal junction
• No prior chemotherapy for gastric cancer except adjuvant and/or neo-adjuvant chemotherapy more than 12 months ago
• Life expectancy of at least 3 months
• Able to take medications orally
• ECOG performance status 0 to 1
• Adequate organ function (bone marrow, kidney and liver)

Exclusion Criteria:

• Certain type(s) of non-measurable lesion(s), if the only one(s).
• Certain serious illness or medical condition(s)
• Lost greater than or equal to 10% of body weight in the 3 months proceeding signing the ICF
• Treatment with drugs interacting with S-1, 5-FU, or cisplatin.
• Pregnant or lactating female.
• Known hypersensitivity to fluoropyrimidines or cisplatin.

Other protocol-defined inclusion/exclusion criteria may apply