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

NCT ID: NCT01470443

Last Updated: 2019-05-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-28
• Study Completion Date: 2020-12-31

Brief Summary

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.

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.

Conditions

Biliary Tract (Intrahepatic, Extrahepatic Cholangiocarcinoma, Gall Bladder) Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GEMOX

• Gemcitabine 1,000 mg/㎡, day 1 and 8, every 3 weeks
• Oxaliplatin 100 mg/㎡, day 1, every 3 weeks

Group Type: ACTIVE_COMPARATOR

Oxaliplatin

Intervention Type: DRUG

Oxaliplatin 100 mg/㎡, day 1, every 3 weeks

XELOX

Xeloda, 1000mg/㎡ bid, day 1-15, every 3 weeks Oxaliplatin 130mg/㎡, day 1, every 3 weeks

Group Type: EXPERIMENTAL

Oxaliplatin

Intervention Type: DRUG

Oxaliplatin 130mg/㎡, day 1, every 3 weeks

Interventions

Oxaliplatin

Oxaliplatin 130mg/㎡, day 1, every 3 weeks

Intervention Type: DRUG

Oxaliplatin

Oxaliplatin 100 mg/㎡, day 1, every 3 weeks

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Samsung Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Ho Yeong Lim

Professor of Medicine, Sungkyunkwan University School of Medicine, Department of Hematology and Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Samsung medical Center

Seoul, , South Korea

Countries

South Korea

References

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.

Reference Type: DERIVED

PMID: 35935821 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30785198 (View on PubMed)

Other Identifiers

2011-05-070

Identifier Type: -

Identifier Source: org_study_id