Phase 2 Study of S-1 in Combination With Cisplatin as 1st Line Therapy in Advanced Non-Small Cell Lung Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00651833|
Recruitment Status : Completed
First Posted : April 3, 2008
Last Update Posted : March 18, 2011
|Condition or disease||Intervention/treatment||Phase|
|Advanced Non-Small Cell Lung Cancer||Drug: S-1||Phase 2|
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 gastrointestinal toxicity.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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)|
|Study Start Date :||February 2005|
|Primary Completion Date :||October 2006|
|Study Completion Date :||July 2007|
All patients will receive S-1 orally at a dose of 25 mg/m2 twice daily (BID) for 14 days followed by a 1-week recovery period, repeated every 3 weeks. Patient will also receive cisplatin, 75 mg/m2 as a 1- to 3-hour infusion on Day 1 of each cycle.
All patients will receive S-1 orally at a dose of 25 mg/m2 twice daily (BID) for 14 days followed by a 1-week recovery period, repeated every 3 weeks. The study may go to the third stage only if 7/31 (23%) or more patients have achieved a confirmed response (CR or PR) in stages 1 and 2 combined.
- Overall tumor response rate (ORR - the proportion of patients with objective evidence of PR or CR) [ Time Frame: 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. ]
- To evaluate the safety profile of S-1 [ Time Frame: AEs will be reported through follow-up (30 days after the last dose of study medication); blood/urine will be collected at baseline ; Days 8 and 15; w/in 24 hrs prior to study drug on Day 1 of each cycle after Cycle 1; at the end of study treatment. ]
- To evaluate the duration of response (DR), and progression-free survival (PFS) [ Time Frame: Each cycle will last 21 days (14 days treatment, 7 days recovery) for a max of 6 cycles. Following discont'n of treatment , pts will be followed for survival status every 2 mos following PD for up to 6 mos. ]
- To investigate the relationship of S-1 plasma levels (components and metabolites) with safety and efficacy parameters [ Time Frame: Each cycle will last 21 days (14 days treatment, 7 days recovery) for a max of 6 cycles. Blood samples to be obtained 1.5 ± 0.5 h, 5 ± 1 h, 7 ± 1 h postdose on Day 1 of Cycle 1 only. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00651833
|Study Director:||Fabio Benedetti, MD||Taiho Oncology, Inc.|