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

Pancreatic Cancer Clinical Trial

— GEST  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00498225
• Other study ID #: 01023017
• Status: Completed
• Phase: Phase 3
• First received: July 6, 2007
• Last updated: November 1, 2012
• Start date: July 2007
• Est. completion date: June 2012

Study information

• Verified date: November 2012
• Source: Taiho Pharmaceutical Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 834
• Est. completion date: June 2012
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 79 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

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.
• 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.
• Gemcitabine
Gemcitabine was administered i.v. by 1000 mg/m2 at day 1, 8, 15 followed by 2 week rest as 1 course.

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Tokyo
Taiwan	Chung-Ho Memorial Hospital, Kaohsiung Medical University	No.100, Tzyou 1st Rd., Kaohsiung
Taiwan	Chang Gung Memorial Hospital, Kaohsiung	No.123, Ta-Pei Rd., Niao-Sung Hsiang, Kaohsiung Hsien
Taiwan	Changhua Christian Hospital	No.135, Nanxiao St., Changhua
Taiwan	National Cheng Kung University Hospital	No.138, Sheng Li Road,Tainan
Taiwan	China Medical University Hospital	No.2, Yuh-Der Rd.,Taichung
Taiwan	Taipei Veterans General Hospital	No.201, Sec. 2, Shih-Pai road, Taipei
Taiwan	Chi Mei Medical Center Liou Ying Campus	No.201, Taikang Village, Liou Ying Township, Tainan
Taiwan	Chang Gung Memorial Hospital, Lonkou	No.5, Fu-Hsing St. Kuei Shan Hsiang, Taoyuan Hsien
Taiwan	National Taiwan University Hospital	No.7, Chung San South Road, Taipei
Taiwan	Chi Mei Medical Center	No.901, Chung Hwa Rd., Yong Kang city, Tainan
Taiwan	Mackay Memorial Hospital, Taipei	No.92, Sec. 2, Zhongshan N. Rd., Taipei

Sponsors (2)

Lead Sponsor	Collaborator
Taiho Pharmaceutical Co., Ltd.	TTY Biopharm

Countries where clinical trial is conducted

Japan,  Taiwan, 

References & Publications (3)

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. — View Citation

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. Epub 2005 Nov 25. — View Citation

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. Epub 2005 Jul 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Over all survival(OS)		every course for first three courses, then every other course	No
Secondary	progression-free survival (PFS), response rate (RECIST, if measurable), incidence rate of adverse events, incidence rate of adverse drug reactions, QOL (EQ-5D)		adverse events will be collected during treatment	Yes