Trial of 3-weekly Versus 5-weekly Schedule of S-1 Plus Cisplatin in Gastric Cancer: SOS
Condition: Advanced Gastric Cancer
MeSH terms: Stomach Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      The urgent need for a new effective therapy with better safety profile for the metastatic
      gastric cancer patients and promising results observed so far in the studies with S-1 plus
      cisplatin combination in advanced gastric cancer (AGC) strongly warrants the comparison of a
      3-weekly schedule to a 5-weekly schedule of S-1 plus cisplatin as a standard regimen in the
      first-line treatment for AGC patients.

      The objectives of this study are to compare a 3-weekly schedule to a 5-weekly schedule of S-1
      plus Cisplatin combination in terms of efficacy, quality of life and safety in patients with
      previously untreated advanced or recurrent unresectable gastric cancer. Primary endpoint is
      progression-free survival. This is an open label, randomized, multi-center,
      non-inferiority/superiority (of 3-weekly regimen over 3-weekly regimen) hybrid study.
    

Detailed description: 
      The primary endpoint of this study is Progression Free Survival (PFS). It is defined as the
      time from the date of randomization to the time of disease progression as assessed by the
      investigators, or death due to any cause. The primary goal of this study is to compare two
      different schedules of S-1 plus cisplatin combination treatments (3-weekly regimen vs.
      5-weekly regimen) for advanced gastric cancer with respect to the PFS based on the hybrid
      design where we can test superiority and non-inferiority in the same trial (Reference:
      Journal of Clinical Oncology 25: 5019-5023, 2007, Boris Freidlin, et el). First, the
      non-inferiority hypothesis will be tested based on the non-inferiority margin 1.15. If the
      inferiority cannot be rejected(meaning non-inferiority is proven) then the superiority will
      be tested. If the superiority test is positive, then superiority is concluded; otherwise
      non-inferiority without superiority will be concluded.

      The sample size was calculated from the following consideration:

      For non-inferiority test: non-inferiority margin 1.15, 10 percent reduction of hazard ratio,
      power 80 percent, alpha 0.025, accrual period 36 months, follow-up period 12 months, and the
      expected median PFS of 6 months for 5 weekly regimen were assumed. Based on the above
      considerations, total of 560 patients will be need. With 10 percent follow-up loss, we need
      622 patients.

      For superiority test: the median PFS for 5-weekly regimen is expected to be 6 months and 7.5
      months for 3-weekly regimen. With sample size of 560 patients calculated above, for detecting
      1.5 months difference in the median PFS between the two groups , we will have 81 percent of
      power, one-sided 5 percent type I error. Using the log rank test assuming exponential
      underlying distribution, accrual period of 36 months, minimum of 12 months follow-up after
      the last enrolment, 516 events will be needed to show the superiority of 3 week cycle.
    

Intervention name(s): S-1 and cisplatin; S-1 and cisplatin
Intervention type(s): Drug; Drug
Intervention description(s): S-1: 80 mg/m2/day po on Days 1-14
cisplatin: 60 mg/m2 iv on Day 1; S-1: 80 mg/day with BSA less than 1.25 m2, 100 mg/day with BSA more than 1.25 m2 and less than 1.5 m2, 120 mg/day with BSA more than 1.5 m2 on Days 1-21 and
cisplatin: 60 mg/m2 iv on Day 1 or 8
Other intervention name(s): TS-1 and cisplatin; TS-1 and cisplatin
Intervention MeSH terms: Cisplatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment