Gemcitabine and S-1 for Advanced Biliary Tract Cancer

Hallym University

Status and phase

Completed

Phase 2

Conditions

Biliary Tract Neoplasm

Treatments

Drug: Gemcitabine, and S-1

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02146703

HMC-HO-GI-0501

Details and patient eligibility

About

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

Full 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.

Enrollment

38 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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