Clinical trial NCT00498225: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pancreatic Cancer
Keywords: Pancreatic Cancer
Lead sponsor: Taiho Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: TTY Biopharm
First posted: 2007-07-09
Enrollment: 834
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Over all survival(OS)
timeFrame: every course for first three courses, then every other course
Secondary outcomes:
measure: progression-free survival (PFS), response rate (RECIST, if measurable), incidence rate of adverse events, incidence rate of adverse drug reactions, QOL (EQ-5D)
timeFrame: adverse events will be collected during treatment
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: No.100, Tzyou 1st Rd., Kaohsiung
country: Taiwan
facility: Chung-Ho Memorial Hospital, Kaohsiung Medical University
city: No.123, Ta-Pei Rd., Niao-Sung Hsiang, Kaohsiung Hsien
country: Taiwan
facility: Chang Gung Memorial Hospital, Kaohsiung
city: No.135, Nanxiao St., Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: No.138, Sheng Li Road,Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: No.2, Yuh-Der Rd.,Taichung
country: Taiwan
facility: China Medical University Hospital
city: No.201, Sec. 2, Shih-Pai road, Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: No.201, Taikang Village, Liou Ying Township, Tainan
country: Taiwan
facility: Chi Mei Medical Center Liou Ying Campus
city: No.5, Fu-Hsing St. Kuei Shan Hsiang, Taoyuan Hsien
country: Taiwan
facility: Chang Gung Memorial Hospital, Lonkou
city: No.7, Chung San South Road, Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: No.901, Chung Hwa Rd., Yong Kang city, Tainan
country: Taiwan
facility: Chi Mei Medical Center
city: No.92, Sec. 2, Zhongshan N. Rd., Taipei
country: Taiwan
facility: Mackay Memorial Hospital, Taipei
Study officials:
affiliation: National Cancer Center Hospital
name: Takuji Okusaka, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. doi: 10.1159/000086771. Epub 2005 Jul 4.
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. doi: 10.1159/000089997. Epub 2005 Nov 25.
citation: 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.
citation: 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.