Study of GEMOX(Gemcitabine/Oxaliplatin) Versus XELOX(Xeloda/Oxaliplatin) in Advanced Biliary Tract Carcinoma

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.

Study Overview

• Status: Unknown
• Conditions: Biliary Tract (Intrahepatic, Extrahepatic Cholangiocarcinoma, Gall Bladder) Cancer
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Oxaliplatin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: GEMOX; Gemcitabine 1,000 mg/㎡, day 1 and 8, every 3 weeks; Oxaliplatin 100 mg/㎡, day 1, every 3 weeks	Drug: Oxaliplatin; Oxaliplatin 130mg/㎡, day 1, every 3 weeks; Drug: Oxaliplatin; Oxaliplatin 100 mg/㎡, day 1, every 3 weeks
EXPERIMENTAL: XELOX; Xeloda, 1000mg/㎡ bid, day 1-15, every 3 weeks Oxaliplatin 130mg/㎡, day 1, every 3 weeks	Drug: Oxaliplatin; Oxaliplatin 130mg/㎡, day 1, every 3 weeks; Drug: Oxaliplatin; Oxaliplatin 100 mg/㎡, day 1, every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival of GEMOX vs XELOX	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.	6 months PFS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profile	physical examination, vital signs, body weight, ECOG performance status, clinical laboratory evaluations (biochemistry, hematology, and urinalysis), and any AE graded by using CTCAE v 4. Data on dose intensity will also be calculated.	6 months follow-up after the last patient registry.

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Publications and helpful links

General Publications

• Chen R, Zhang Y, Lin K, Huang D, You M, Lai Y, Wang J, Hu Y, Li N. Cost-Effectiveness Analysis of Capecitabine Plus Oxaliplatin Versus Gemcitabine Plus Oxaliplatin as First-Line Therapy for Advanced Biliary Tract Cancers. Front Pharmacol. 2022 Jul 22;13:871262. doi: 10.3389/fphar.2022.871262. eCollection 2022.
• Kim ST, Kang JH, Lee J, Lee HW, Oh SY, Jang JS, Lee MA, Sohn BS, Yoon SY, Choi HJ, Hong JH, Kim MJ, Kim S, Park YS, Park JO, Lim HY. Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial. Ann Oncol. 2019 May 1;30(5):788-795. doi: 10.1093/annonc/mdz058.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 28, 2011
• Primary Completion (ACTUAL): December 1, 2016
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: November 9, 2011
• First Submitted That Met QC Criteria: November 10, 2011
• First Posted (ESTIMATE): November 11, 2011

Study Record Updates

• Last Update Posted (ACTUAL): May 21, 2019
• Last Update Submitted That Met QC Criteria: May 17, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Antineoplastic Agents; Oxaliplatin
• Other Study ID Numbers: 2011-05-070