Biliary Tract Neoplasm
Conditions
Keywords
biliary tract neoplasm, gemcitabine, S-1
Brief summary
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
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.
Interventions
DRUGGemcitabine, and S-1
Treatment will be delivered as a 3-week cycle. 1. Gemcitabine 1000 mg/m2 iv on day 1, 8 2. S-1 60 mg/day po on day 1-14
Sponsors
Jeil Pharmaceutical Co., Ltd.
Hallym University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective reponse rate | 1 year |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival, median overall survival, disease control rate, and over grade 3 hematologic toxicities (neutropenia, thrombocytopenia, and febrile neutropenia) | 1 year |
Countries
South Korea
Outcome results
None listed