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
18 Years
N/A
Both
Biliary Tract (Intrahepatic, Extrahepatic Cholangiocarcinoma, Gall Bladder) Cancer
Trial Information
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
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.
Inclusion Criteria
Inclusion criteria
1. age ≥ 18
2. histologically or cytologically confirmed adenocarcinoma of biliary tract
(intrahepatic, extrahepatic cholangiocarcinoma, gall bladder cancer.however, ampulla
of vater cancer is excluded)
3. unresectable or metastatic
4. ECOG performance status of 0~2
5. measurable or evaluable lesion per RECIST 1.1 criteria
6. Life expectancy≥12weeks
7. Adequate marrow, hepatic, renal and cardiac functions Serum aspartate transaminase
and serum alanine transaminase≤ 2.5 x upper limit of normal (ULN), or AST and ALT ≤ 5
x ULN if liver function abnormalities are due to underlying malignancy Total serum
bilirubin ≤ 1.5 x ULN Absolute neutrophil count(ANC) ≥ 1,500/uL Platelets ≥
100,0000/uL Hemoglobin ≥ 8.0 g/dL
8. chemotherapy naïve patient: prior adjuvant chemoradiation or chemotherapy is allowed
if the last date of drug administration is > 6 months from the study entry date
9. provision of a signed written informed consent
Exclusion criteria
1. severe co-morbid illness and/or active infections
2. ampulla of vater cancer is excluded
3. pregnant or lactating women
4. Active CNS metastases not controllable with radiotherapy or corticosteroids
(however,CNS metastases(except for leptomeningeal seeding) are allowed if controlled
by gamma knife surgery or surgery or radiotherapy or steroid)
5. known history of hypersensitivity to study drugs
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression free survival of GEMOX vs XELOX
Outcome Description:
reference 6 months PFS 50% (GEMOX arm), noninferiority 6 months PFS 35% (XELOX arm), 1:1 randomization, accrual 24 months, 6 months follow-up after the last patient registry.
Outcome Time Frame:
6 months PFS
Safety Issue:
No
Authority:
Korea: Food and Drug Administration
Study ID:
2011-05-070
NCT ID:
NCT01470443
Start Date:
December 2011
Completion Date:
Related Keywords:
- Biliary Tract (Intrahepatic, Extrahepatic Cholangiocarcinoma, Gall Bladder) Cancer
- Carcinoma
- Cholangiocarcinoma
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