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

Study Overview
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Brief Summary
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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.

Official Title
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Randomized Phase III Study of Gemcitabine Versus TS-1 Versus Gemcitabine Plus TS-1 in Unresectable Advanced Pancreatic Cancer (With Local Progression or Metastasis)

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Gemcitabine plus TS-1
* Drug: TS-1
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Gemcitabine plus TS-1 | Drug: Gemcitabine plus TS-1<br>* 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.<br>|
| Experimental: 2<br>TS-1 | Drug: TS-1<br>* TS-1 was administered orally at 40 mg/m2 twice daily for 28 days with a rest period of 2week as one course.<br>|
| Active Comparator: 3<br>Gemcitabine | Drug: Gemcitabine<br>* Gemcitabine was administered i.v. by 1000 mg/m2 at day 1, 8, 15 followed by 2 week rest as 1 course.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Over all survival(OS) |  | every course for first three courses, then every other course | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatic Cancer