Phase 2 Study of S-1 in Advanced or Metastatic Pancreatic Cancer
The purpose of this study is to determine whether S-1 is effective in slowing tumor activity in patients with locally advanced or metastatic pancreatic cancer who have not had chemotherapy. The study is also looking at the safety of S-1.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-Label, Non-Randomized, Multicenter, Two-Stage, Phase 2 Study of S-1 in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Pancreatic Cancer|
- 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 1 year, unless patient is still on treatment, or at the time of death, whichever occurs first. Tumor assessments will be obtained at baseline and at the end of every even cycle. ] [ Designated as safety issue: No ]
- To evaluate the disease control rate (DCR), duration of response (DR), time to tumor progression (TTP), and survival rate [ Time Frame: Each cycle will last 21 days (14 days treatment, 7 days recovery) for 1 yr, unless pt is still on treatment, or at the time of death. Pts will be followed for survival status every 2 mos following PD for up to 1 yr ] [ Designated as safety issue: No ]
- To investigate the effect of S-1 on Karnofsky Performance Status (KPS) and pain assessments, including pain intensity and analgesic consumption [ Time Frame: Each cycle will last 21 days for up to 1 yr. KPS measured at baseline; w/in 24 hrs prior to drug (Day 1) for cycles after Cycle 1; end of treatment. Pts complete pain diary at 7 days prior to Day 1 of Cycle 1 and cont'ing through end of treatment. ] [ Designated as safety issue: No ]
- To evaluate the safety profile of S-1 [ Time Frame: AEs will be reported through f/up ; blood/urine will be collected at baseline, Days 8&15, w/in 24 hrs of study drug on Day 1 of each cycle after Cycle 1; at end of study treatment ] [ Designated as safety issue: Yes ]
- 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 reatment, 7 days recovery). Blood samples to be obtained 1.5 ± 0.5 h, 5 ± 1 h, 7 ± 1 h postdose on Day 1 of Cycle 1 only ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2006|
|Study Completion Date:||October 2008|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
All patients will receive S-1 orally at a dose of 30 mg/m2 twice daily (BID) for 14 days followed by a 1-week recovery period, repeated every 3 weeks.
All patients will receive S-1 orally at a dose of 30 mg/m2 twice daily (BID) for 14 days followed by a 1-week recovery period, repeated every 3 weeks. The trial will proceed to the second stage only if sufficient efficacy is demonstrated in Stage 1.
Locally advanced or metastatic pancreatic 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.