Gemcitabine and S-1 for Advanced Biliary Tract Cancer

Study Overview
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Brief Summary
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This study will conduct a phase II study of gemcitabine and S-1 as first-line chemotherapy in patient with advanced biliary tract cancer

Detailed Description
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Biliary-tract cancer (BTC) is invasive carcinoma that originates from the epithelial lining of the gallbladder and bile ducts. BTC include cholangiocarcinoma (intrahepatic, perihilar, and distal biliary-tree tumor) and carcinoma arising from the gallbladder. Surgical resection of the primary tumor is potentially curative for BTC, but less than a quarter of patients are eligible for resection at presentation. Systemic chemotherapy is the principal treatment method for patients with unresectable or metastatic BTC. Gemcitabine is a promising agent, which has shown efficacy in biliary tract cancer. As a single-agent therapy, gemcitabine shows response rates of 8-36% in BTC[4]. In phase II trials with patients in advanced BTC, gemcitabine in combination with capecitabine or platinum analogues produced objective response rates of 26-50%. The ABC-02 study reported a significant survival advantage for gemcitabine and cisplatin over gemcitabine alone in patients with advanced BTC (median overall survival 11.7 vs. 8.1 months; P < 0.001). Oral anticancer drug S-1 consists of the 5-FU prodrug tegafur with two biochemical modulators, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo). S-1 monotherapy is active against advanced BTC with objective response rates of 21-35%, and phase II trials of S-1 in combination with gemcitabine reported objective response rates of 20-36%. Differences between trials in the doses and administration schedules of gemcitabine and S-1 may be reflected in the ranges of efficacy, dose-intensity, and rates of toxicity observed. Even though the efficacy of gemcitabine and S-1 combination is evident for patients with advanced BTC in previous phase II trials, there was no clinical study investigating the efficacy of gemcitabine and S-1 combination for patients with advanced BTC when this study was started. Therefore, we conducted a phase II study to evaluate gemcitabine and S-1 combination as first-line chemotherapy for patients with advanced BTC.

Official Title
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Phase II Trial of Gemcitabine and S-1 for Patients With Advanced Biliary Tract Cancer

Conditions
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Biliary Tract Neoplasm

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable, locally advanced, metastatic adenocarcinoma arising from the intra- and extrahepatic biliary ducts or gallbladder Initially diagnosed or recurred At least one bidimensionally measurable lesion, defined as at least 1x1cm with clearly defined margins on physical examination, on 3-dimentional CT, MRI, or PET-CT Age ≥18 and ≤70 years Estimated life expectancy ≥3 months ECOG performance status ≤2 Adequate bone marrow function (WBCs ≥4,000/µL or absolute neutrophil count ≥1,500/µL, platelets ≥100,000/µL), Adequate kidney function (creatinine ≤1.4 mg/dL) Adequate liver function (bilirubin ≤1.8 mg/dL, transaminase levels ≤100mg/dL) Written informed consent Exclusion Criteria: Other tumor type than adenocarcinoma Previous history of chemotherapy (exception : adjuvant chemotherapy) Presence of CNS metastasis, psychosis, or seizure Obvious bowel obstruction Evidence of serious gastrointestinal bleeding Past or concurrent history of neoplasm other than biliary adenocarcinoma, except for curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix uteri Pregnant or lactating women, women of childbearing potential not employing adequate contraception Other serious illness or medical conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: gemcitabine and S-1<br> | Drug: Gemcitabine, and S-1<br>* Treatment will be delivered as a 3-week cycle. Gemcitabine 1000 mg/m2 iv on day 1, 8 S-1 60 mg/day po on day 1-14<br>* Other names: TS-1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective reponse rate |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival, median overall survival, disease control rate, and over grade 3 hematologic toxicities (neutropenia, thrombocytopenia, and febrile neutropenia) |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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biliary tract neoplasm, gemcitabine, S-1