Biomarker Discovery in Patients With Advanced Biliary Tract Cancer

NCT ID: NCT04871321

Last Updated: 2025-08-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

119 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-04-14

Study Completion Date

2023-12-31

Brief Summary

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Biliary tract cancer is a rare gastrointestinal malignant neoplasm and includes intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gall bladder cancer. Curative surgical resection offers the only chance for cure. However, most patients with BTC are diagnosed at an unresectable stage. Therefore, the survival outcomes of patients with advanced biliary tract cancer remain dismal.

The combination of gemcitabine and cisplatin has become the current standard for advanced BTCs since the landmark ABC-02 trial in 2010. However, the median overall survival of Gem/Cis chemotherapy is less than 1 year. Recently, a triplet regimen of gemcitabine, cisplatin, and nab-paclitaxel showed promising results in a single-arm phase II multicenter study.

However, biliary tract cancer is a group of heterogenous diseases by site and genetic alteration, and this diversity may lead differences in response to systemic chemotherapy.

Transcriptome analysis through RNA-sequencing has rarely been performed in advanced biliary tract cancer, and even if it has performed, only small number of patients were included. Further research on multi-omics data is needed on the necessity and clinical significance in treatment of biliary tract cancer.

Detailed Description

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Using biopsy specimen (formalin fixed paraffin embedded tissue), in-house NGS and RNA-sequencing will be performed simultaneously. Through this, investigators will discover biomarkers based on multi-omics data that predict response to systemic chemotherapy (nab-paclitaxel plus gemcitabine-cisplatin). In addition, blood sampling will be performed in parallel to conduct research on cell-free DNA and circulating tumor cell analysis related to response and progression on chemotherapy; before administration of chemotherapy, 3 months after chemotherapy, 6 months after chemotherapy, the time of disease progression (if possible), before curative resection (if possible).

Conditions

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Biliary Tract Cancer Cholangiocarcinoma Gallbladder Cancer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Gem/Cis/nab-P

Gemcitabine + Cisplatin + Nab-Paciltaxel

nab-paclitaxel plus gemcitabine-cisplatin

Intervention Type DRUG

\- gemcitabine 800mg/m2 + cisplatin 25 mg/m2 + nab-paclitaxel 100mg/m2 on day 1 and day 8, every 21 days

Interventions

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nab-paclitaxel plus gemcitabine-cisplatin

\- gemcitabine 800mg/m2 + cisplatin 25 mg/m2 + nab-paclitaxel 100mg/m2 on day 1 and day 8, every 21 days

Intervention Type DRUG

Other Intervention Names

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immunohistochemistry, NGS, RNA-sequencing, Liquid biopsy

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 19 years old
* Capable of understanding and complying with the protocol requirements and signed informed consent
* The patients were confirmed as bilary tract cancer (gall bladder cancer, extrahepatic cholangiocarcinoma, intrahepatic cholangiocarcinoma) by histopathology or cytology
* Patients with inoperable or metastatic or recurrent biliary tract cancer
* Patients who underwent in-house next-generation sequencing
* Patients planning to receive Gemcitabine, Cisplatin, nab-paclitaxel triplet chemotherapy
* At least one measurable objective lesion was identified based on the RECIST 1.1 criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* The expected survival a ≥3 months

Exclusion Criteria

* The subject has uncontrolled, significant intercurrent or recent illness including infection for organ failure
* Prior palliative chemotherapy for biliary tract cancer
* Dementia, altered mental state, or any mental illness that prevents understanding or informed consent
* Other conditions that researchers not think to be suitable for enrollment.
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dong-A Pharmaceutical

INDUSTRY

Sponsor Role collaborator

CHA University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hongjae Chon, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

CHA University

Locations

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CHA Bundang Medical Center

Seongnam-si, Gyeonggi-do, South Korea

Site Status

Countries

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South Korea

References

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Jarnagin WR, Fong Y, DeMatteo RP, Gonen M, Burke EC, Bodniewicz BS J, Youssef BA M, Klimstra D, Blumgart LH. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg. 2001 Oct;234(4):507-17; discussion 517-9. doi: 10.1097/00000658-200110000-00010.

Reference Type BACKGROUND
PMID: 11573044 (View on PubMed)

Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.

Reference Type BACKGROUND
PMID: 20375404 (View on PubMed)

Kim BJ, Hyung J, Yoo C, Kim KP, Park SJ, Lee SS, Park DH, Song TJ, Seo DW, Lee SK, Kim MH, Park JH, Cho H, Ryoo BY, Chang HM. Prognostic factors in patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin: retrospective analysis of 740 patients. Cancer Chemother Pharmacol. 2017 Jul;80(1):209-215. doi: 10.1007/s00280-017-3353-2. Epub 2017 Jun 8.

Reference Type BACKGROUND
PMID: 28597043 (View on PubMed)

Shroff RT, Javle MM, Xiao L, Kaseb AO, Varadhachary GR, Wolff RA, Raghav KPS, Iwasaki M, Masci P, Ramanathan RK, Ahn DH, Bekaii-Saab TS, Borad MJ. Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):824-830. doi: 10.1001/jamaoncol.2019.0270.

Reference Type BACKGROUND
PMID: 30998813 (View on PubMed)

Chae H, Kim D, Yoo C, Kim KP, Jeong JH, Chang HM, Lee SS, Park DH, Song TJ, Hwang S, Kim KH, Song GW, Ahn CS, Lee JH, Hwang DW, Kim SC, Jang SJ, Hong SM, Kim TW, Ryoo BY. Therapeutic relevance of targeted sequencing in management of patients with advanced biliary tract cancer: DNA damage repair gene mutations as a predictive biomarker. Eur J Cancer. 2019 Oct;120:31-39. doi: 10.1016/j.ejca.2019.07.022. Epub 2019 Aug 30.

Reference Type BACKGROUND
PMID: 31476489 (View on PubMed)

Nakamura H, Arai Y, Totoki Y, Shirota T, Elzawahry A, Kato M, Hama N, Hosoda F, Urushidate T, Ohashi S, Hiraoka N, Ojima H, Shimada K, Okusaka T, Kosuge T, Miyagawa S, Shibata T. Genomic spectra of biliary tract cancer. Nat Genet. 2015 Sep;47(9):1003-10. doi: 10.1038/ng.3375. Epub 2015 Aug 10.

Reference Type BACKGROUND
PMID: 26258846 (View on PubMed)

Chu KJ, Ma YS, Jiang XH, Wu TM, Wu ZJ, Li ZZ, Wang JH, Gao QX, Yi B, Shi Y, Wang HM, Gu LP, Zhang SQ, Wang GR, Liu JB, Fu D, Jiang XQ. Whole-Transcriptome Sequencing Identifies Key Differentially Expressed mRNAs, miRNAs, lncRNAs, and circRNAs Associated with CHOL. Mol Ther Nucleic Acids. 2020 Sep 4;21:592-603. doi: 10.1016/j.omtn.2020.06.025. Epub 2020 Jun 27.

Reference Type BACKGROUND
PMID: 32721879 (View on PubMed)

Cheon J, Lee CK, Sang YB, Choi HJ, Kim MH, Ji JH, Ko KH, Kwon CI, Kim DJ, Choi SH, Kim C, Kang B, Chon HJ. Real-world efficacy and safety of nab-paclitaxel plus gemcitabine-cisplatin in patients with advanced biliary tract cancers: a multicenter retrospective analysis. Ther Adv Med Oncol. 2021 Aug 7;13:17588359211035983. doi: 10.1177/17588359211035983. eCollection 2021.

Reference Type BACKGROUND
PMID: 34394748 (View on PubMed)

Other Identifiers

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2021-03-045

Identifier Type: -

Identifier Source: org_study_id

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