Phase II Study of Gemcitabine Versus S-1 Adjuvant Therapy After Hemihepatectomy for Biliary Tract Cancer

Study Overview
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Brief Summary
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To compare efficacy and safety of Gemcitabine versus S-1 adjuvant therapy after hemihepatectomy.

Detailed Description
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There is no standard adjuvant therapy after liver hemi-hepatectomy due to bile duct cancer, because of high surgical morbidity ratio and high adverse event ratio of adjuvant therapy. For example, our preliminary results showed that regular gemcitabine administration (1000mg/m2, day 1, 8, 15 every 4 weeks) after hemihepatectomy was too toxic and induced severe leukocytopenia and/or thrombocytopenia. Formerly, the investigators planned the study to decide more safety adjuvant protocol (recommend dose: RD) for Gemcitabine or S-1 after hemihepatectomy using Continuous Reassessment Method (CRM) analysis and decided the recommend doses. Note: In the former study, the investigators decided that tolerable ratio of Dose Limiting Toxicity (DLT) would be less than 10%. Herein, the investigators planned the study to evaluate efficacy (recurrent free survival as primary outcome, and overall-survival as secondary outcome) and safety (as secondary outcome) in our recommended protocols, and to compare the efficacy as randomized control trial.

Official Title
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Randomized Phase II Study of Gemcitabine Versus S-1 Adjuvant Therapy After Hemihepatectomy for Biliary Tract Cancer

Conditions
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Biliary Tract Cancer

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: S-1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biliary tract cancer (BTC) (>= Unio Internationalis Contra Cancrum (UICC) Stage IB), adenocarcinoma R0 or R1 resection no obvious recurrent lesion 20 years old or more Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1 The patient underwent no other treatment than surgery for BTC Neutrophil must be over 1500/μl, Hemoglobin must be over 9.0g/dL, platelet must be over 100,000/μl, Aspartate transaminase (AST) and Alanine aminotransferase (ALT) must be less than 150 IU/L, total bilirubin must be less than 1.5 mg/dL, Creatinine must be less than 1.2 mg/dl, and Creatinine clearance must be over 60 mL/min The patient can intake drugs per os. From 4 to 12 weeks after the surgery Written informed consent Exclusion Criteria: Existence of active double cancer The patient suffered from severe drug allergy Sever complications (interstitial pneumonia, heart failure, renal failure, liver failure, ileus, incontrollable diabetes mellitus, and so on) Any active infections exist. Pregnancy Severe mental disorder Others

Ages Eligible for Study
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Minimum Age: 20 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: Gemcitabine group<br>1000mg/m2, day 1 every 2 weeks | Drug: Gemcitabine<br>* 1000mg/m2, day 1 every 2 weeks<br>* Other names: gemzer;|
| Experimental: S-1 group<br>80mg/m2/day, day 1-28, every 6 weeks | Drug: S-1<br>* 80mg/m2/day, day 1-28, every 6 weeks<br>* Other names: TS-1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1 year recurrent free survival rate | Duration: From randomization to evidenced recurrence or death. Rate: Number of patients with evidenced recurrence or death / number of total patients. 1 year recurrent free survival rate: recurrent free survival rate at one-year from the randomization | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Two-year recurrent free survival rate |  | Two years | 
| One-year overall survival rate |  | One year | 
| Two-year overall survival rate |  | Two years | 
| Completion rate of the protocol treatment |  | 6 months | 
| Dose intensity of anti-tumor drugs |  | 6 months | 
| Rate and grade of adverse events or adverse drug reactions |  | 6 months | 
| Duration of recurrent free survival |  | an expected average of 2 years | 
| Duration of overall survival |  | an expected average of 3 years |