Phase III of Gemcitabine Vs TS-1 Vs Gemcitabine Plus TS-1 in Pancreatic Cancer (GEST)

• ClinicalTrials.gov Identifier: NCT00498225
• Recruitment Status: Completed
• First Posted: July 9, 2007
• Last Update Posted: November 2, 2012
• Sponsor: Taiho Pharmaceutical Co., Ltd.
• Collaborator: TTY Biopharm
• Information provided by (Responsible Party): Taiho Pharmaceutical Co., Ltd.

Tracking Information

• First Submitted Date: July 6, 2007
• First Posted Date: July 9, 2007
• Last Update Posted Date: November 2, 2012
• Study Start Date: July 2007
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 1, 2008): Over all survival(OS) [ Time Frame: every course for first three courses, then every other course ]
• Original Primary Outcome Measures (submitted: July 6, 2007): Over all survival(OS)
• Current Secondary Outcome Measures (submitted: July 1, 2008): progression-free survival (PFS), response rate (RECIST, if measurable), incidence rate of adverse events, incidence rate of adverse drug reactions, QOL (EQ-5D) [ Time Frame: adverse events will be collected during treatment ]
• Original Secondary Outcome Measures (submitted: July 6, 2007): progression-free survival (PFS), response rate (RECIST, if measurable), incidence rate of adverse events, incidence rate of adverse drug reactions, QOL (EQ-5D)
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase III of Gemcitabine Vs TS-1 Vs Gemcitabine Plus TS-1 in Pancreatic Cancer
• Official Title: Randomized Phase III Study of Gemcitabine Versus TS-1 Versus Gemcitabine Plus TS-1 in Unresectable Advanced Pancreatic Cancer (With Local Progression or Metastasis)
• Brief Summary: In patients with unresectable advanced pancreatic cancer, non-inferiority of TS-1 monotherapy and superiority of GEM + TS-1 combination therapy to gemcitabine (GEM) will be verified using survival time.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pancreatic Cancer

Intervention

• Drug: Gemcitabine plus TS-1
  Gemcitabine plus TS-1:Gemcitabine was administered i.v. by 1000 mg/m2 at day 1, 8 followed by 2 week rest as 1 course. TS-1 was co-administered orally at 40 mg/m2 twice daily for 14 days with a rest period of 1 week as one course.
• Drug: TS-1
  TS-1 was administered orally at 40 mg/m2 twice daily for 28 days with a rest period of 2week as one course.
• Drug: Gemcitabine
  Gemcitabine was administered i.v. by 1000 mg/m2 at day 1, 8, 15 followed by 2 week rest as 1 course.

Study Arms

• Experimental: 1
  Gemcitabine plus TS-1
  Intervention: Drug: Gemcitabine plus TS-1
• Experimental: 2
  TS-1
  Intervention: Drug: TS-1
• Active Comparator: 3
  Gemcitabine
  Intervention: Drug: Gemcitabine

Publications *

• Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. doi: 10.1200/JCO.1997.15.6.2403.
• Ueno H, Okusaka T, Ikeda M, Takezako Y, Morizane C. An early phase II study of S-1 in patients with metastatic pancreatic cancer. Oncology. 2005;68(2-3):171-8. doi: 10.1159/000086771. Epub 2005 Jul 4.
• Ueno H, Okusaka T, Ikeda M, Ishiguro Y, Morizane C, Matsubara J, Furuse J, Ishii H, Nagase M, Nakachi K. A phase I study of combination chemotherapy with gemcitabine and oral S-1 for advanced pancreatic cancer. Oncology. 2005;69(5):421-7. doi: 10.1159/000089997. Epub 2005 Nov 25.
• Okusaka T, Miyakawa H, Fujii H, Nakamori S, Satoh T, Hamamoto Y, Ito T, Maguchi H, Matsumoto S, Ueno H, Ioka T, Boku N, Egawa S, Hatori T, Furuse J, Mizumoto K, Ohkawa S, Yamaguchi T, Yamao K, Funakoshi A, Chen JS, Cheng AL, Sato A, Ohashi Y, Tanaka M; GEST group. Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer. J Cancer Res Clin Oncol. 2017 Jun;143(6):1053-1059. doi: 10.1007/s00432-017-2349-y. Epub 2017 Feb 16.
• Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013 May 1;31(13):1640-8. doi: 10.1200/JCO.2012.43.3680. Epub 2013 Apr 1.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 1, 2012): 834
• Original Estimated Enrollment (submitted: July 6, 2007): 600
• Actual Study Completion Date: June 2012
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Pancreatic carcinoma histologically determined to be adenocarcinoma or adenosquamous carcinoma.
• Advanced unresectable pancreatic (including pancreatic cancer with local progression and recurrent pancreatic cancer).Presence/absence of measurable lesions is not considered. Patients with measurable lesions must undergo diagnostic imaging tests within 28 days before registration.
• Patients with no previous treatment (radiotherapy,chemotherapy etc) for pancreatic cancer, except resection. Intra-operative radiotherapy during resection of pancreatic cancer will be permitted, although registration must occur at least 4 weeks after the radiotherapy. Patients that have undergone preoperative/postoperative adjuvant chemotherapy may be enrolled if relapse is diagnosed beyond week 24 after the final administration (on day 169 when the day following the final day is set as day 1).
• Age: 20 years to 79 years.
• ECOG Performance Status (PS) of 0 or 1.
• Sufficient function of major organs as defined below. (The following criteria are satisfied in laboratory tests conducted within 14 days before registration. Laboratory tests conducted 2 weeks before registration (on the same weekday) will be included.) White blood cell count≥ 3500/mm3 Neutrophil count≥ 2000/mm3 Hemoglobin≥9.0 g/dL Platelet count≥100000/mm3 Total bilirubin≤ 2.0 mg/dL* *≤ 3.0 mg/dL in patients treated by biliary drainage for obstructive jaundice. AST and ALT≤ 150 U/L Serum creatinine≤1.2 mg/dL Creatinine clearance≥50mL/min.** **Measured values will be used if available. Otherwise, values calculated by the Cockcroft-Gault method will be used.Formula for estimation:body weight (kg) x [140 - age (years) / 72 x serum creatinine (mg/dL)] *Estimated value will be multiplied by 0.85 for females.
• Able to take capsules orally.
• No clinically abnormal ECG findings within 28 days (4 weeks)before registration.
• Voluntarily signed the written consent form.

Exclusion Criteria:

• Pulmonary fibrosis or interstitial pneumonia (to be confirmed by chest X-ray within 28 days before enrollment).
• Watery diarrhoea.
• Active infections (e.g. patients with pyrexia of 38°C or greater), excluding viral hepatitis.
• Serious complications (e.g. heart failure, renal failure,hepatic failure, haemorrhagic peptic ulcer, intestinal paralysis, intestinal obstruction or poorly controlled diabetes).
• Moderate or severe (requiring drainage) ascites or pleural effusion requiring treatment.
• Metastasis in the CNS.
• Active double cancer (synchronous double cancer or asynchronous double cancer with disease-free duration of 3 years or less). Carcinoma in situ and lesions of intramucosal carcinoma will not be included in active double cancer and will be permitted for registration.
• Patients under treatment with flucytosine, phenytoin or warfarin potassium.
• Pregnant females, possibly pregnant females, females wishing to become pregnant and nursing mothers. Males that are currently attempting to produce a pregnancy.
• Severe mental disorder.
• Judged ineligible by physicians for participation in the study from a safety viewpoint.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 79 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan, Taiwan

Administrative Information

• NCT Number: NCT00498225
• Other Study ID Numbers: 01023017
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Taiho Pharmaceutical Co., Ltd.
• Original Responsible Party: Not Provided
• Current Study Sponsor: Taiho Pharmaceutical Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: TTY Biopharm

Investigators

• Principal Investigator: Takuji Okusaka, MD; National Cancer Center Hospital

• PRS Account: Taiho Pharmaceutical Co., Ltd.
• Verification Date: November 2012