An Open-Label, Non-Randomized, Multicenter, Three-Stage, Phase 2 Study of S-1 in Combination With Cisplatin as 1st Line Therapy for Patients With Advanced Non-Small Cell Lung Cancer (Stage IIIB/Stage IV)
Advanced non-small cell lung cancer is relatively unresponsive to chemotherapy. This is true
for the nucleoside analogue gemcitabine, with a response rate of approximately 10%, as well
as for 5-fluorouracil (5-FU). Even when gemcitabine is combined with other chemotherapeutic
drugs or biological agents, the overall tumor response rate remains basically unchanged.
S-1 is a new generation oral fluoropyrimidine that combines Tegafur
(5-fluoro-1-(tetrahydro-2-furanyl)-2,4(1H,3H)-pyrimidinedione [FT]), an oral prodrug of
5-FU, with two modulators, Gimeracil (5-chloro-2,4-dihydroxypyridine [CDHP]), which inhibits
5-FU degradation by dihydropyrimidine dehydrogenase (DPD) inhibition, and Oteracil potassium
(Oxo), which inhibits 5-FU phosphorylation in the digestive tract. This combination of 3
compounds is designed to achieve enhanced antitumor activity while decreasing
This is an open-label, multicenter, single-arm, 3-stage, Phase 2 study evaluating the
efficacy and safety of S-1 in combination with cisplatin as 1st line therapy for patients
with advanced NSCLC. The 3 stages of this study correspond to a run-in tolerability stage
(stage 1), futility stage (stage 2), and decision stage (stage 3). The run-in tolerability
stage will be conducted to assess any additional toxicity associated with a more frequent
schedule of administration of cisplatin (75 mg/m2 every 3 weeks) compared with the dosing
regimen established in a prior Phase I study in patients with advanced gastric cancer (75
mg/m2 every 4 weeks). The futility stage (stage 2) will be conducted to ensure that this
treatment combination is sufficiently efficacious to expose a sufficient number of patients
to be able to make a decision (stage 3) on whether this combination treatment warrants
further evaluation in future studies.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall tumor response rate (ORR - the proportion of patients with objective evidence of PR or CR)
Each cycle will last 21 days (14 days treatment, 7 days recovery) for a max of 6 cycles. Tumor assessments will be obtained at baseline and at the end of every even cycle.
Fabio Benedetti, MD
Taiho Pharma USA, Inc.
United States: Food and Drug Administration