Biliary Tract (Intrahepatic, Extrahepatic Cholangiocarcinoma, Gall Bladder) Cancer Clinical Trial
Official title:
A Randomized, Multicenter, Open-label, Phase 3 Study to Compare the Efficacy and Safety of GEMOX(Gemcitabine/Oxaliplatin) vs XELOX(Xeloda/Oxaliplatin) in Advanced Biliary Tract Carcinoma
The objective of the trial is to compare Progression free survival between GEMOX (gemcitabine/oxaliplatin)vs XELOX(capecitabine/oxaliplatin)in metastatic or unresectable Biliary tract carcinoma patients.
In patients with advanced BTC(biliary tract cancer), either gemcitabine-based, 5-FU-based
chemotherapy or clinical trial is recommended as first-line treatment. According to ABC-02
trial, as compared with gemcitabine alone, cisplatin plus gemcitabine was associated with a
significant survival advantage without the addition of substantial toxicity. Cisplatin plus
gemcitabine is an appropriate option for the treatment of patients with advanced biliary
cancer. (ClinicalTrials.gov number, NCT00262769.) Recent metaanalysis [7], analyzed 104 phase
II and III trials comprising 2810 BTC patients and found that gemcitabine combined with
platinum compounds such as cisplatin or oxaliplatin had superior response rate and survival
when compared with gemcitabine alone. The metaanalysis concluded the combination of
gemcitabine and cisplatin or oxaliplatin to be the reference arm for future clinical trials.
Meanwhile, oxaliplatin (l-OHP), an alkylating diaminocyclohexane platinum derivate, has been
noted to display a marked cytotoxic synergism in combination with fluoropyrimidines against a
variety of solid human tumour cells [11]. Based on these information, Nehls et al. [12]
conducted a prospective phase II study of oxaliplatin plus 5-FU/folinic acid in biliary
system adenocarcinomas, and the disease control rate (responses and stable disease (SD)) was
56%, and the median OS was 9.5 months. To improve efficacy and to offer a more convenient
treatment option for patients by reducing clinical visits and avoiding indwelling devices,
they prospectively investigated the activity and toxicity profile of three-weekly intravenous
oxaliplatin plus oral capecitabine (XELOX), and concluded that the XELOX regimen was a
well-tolerated and active treatment option for advanced BTC [13].
Given a lack of prospective, direct, comparison between XELOX and GEMOX regimens in advanced
BTC, we propose a randomized phase III trial of GEMOX (gemcitabine/oxaliplatin) vs XELOX
(capecitabine/oxaliplatin) in metastatic or unresectable BTC patients.
With the assumption of a median 6-month PFS rate of 50% in the GEMOX arm and 35% in the XELOX
arm (non-inferiority margin, 15%), a total of 103 patients were required under a two-sided 5%
significance level and 80% power, with an accrual of 59 months and a follow-up of 6 months
after the last patient registry, to show the non-inferiority of XELOX to GEMOX. An
exponential distribution of time to progression was assumed. Allowing a dropout rate of 10%,
we aimed to enroll 230 patients. An interim analysis was not planned.
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