Biomarker Discovery in Patients With Advanced Biliary Tract Cancer

NCT04871321 | Completed

• 1 other identifier: 2021-03-045
• Study Type: observational
• Target: 119
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Biliary Tract Cancer; Cholangiocarcinoma; Gallbladder Cancer

Keywords

Biliary Tract cancer; Gemcitabine; Cisplatin; nab-paclitaxel; RNA sequencing; biomarker

Outcome Measures

Primary Outcomes (2)

• collected tumor samples

  tumor samples from patients with hepatobiliary cancers (incidence of genetic alteration, association with treatment response and survival duration)

  through study completion, an average of 2 years

• collected blood samples

  blood samples from patients with hepatobiliary cancers (incidence of genetic alteration, association with treatment response and survival duration)

  through study completion, an average of 2 years

Secondary Outcomes (2)

• Multi-omics analysis

  2 years

• Biomarkers on the efficacy of Gemcitabine/Cisplatin/Nab-paclitaxel for advanced biliary tract cancer

  2 years

Study Arms (1)

Gem/Cis/nab-P

Gemcitabine + Cisplatin + Nab-Paciltaxel

Drug: nab-paclitaxel plus gemcitabine-cisplatin

Interventions

nab-paclitaxel plus gemcitabine-cisplatin DRUG

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

Also known as: immunohistochemistry, NGS, RNA-sequencing, Liquid biopsy

Gem/Cis/nab-P

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with advanced biliary tract cancer will be recruited at CHA Bundang Medical Center

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• CHA University: lead
• Dong-A Pharmaceutical: collaborator

Study Sites (1)

CHA Bundang Medical Center

Seongnam-si, Gyeonggi-do, 13496, South Korea

Location

Related Publications (8)

• 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.

  PMID: 11573044 BACKGROUND

• 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.

  PMID: 20375404 BACKGROUND

• 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.

  PMID: 28597043 BACKGROUND

• 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.

  PMID: 30998813 BACKGROUND

• 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.

  PMID: 31476489 BACKGROUND

• 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.

  PMID: 26258846 BACKGROUND

• 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.

  PMID: 32721879 BACKGROUND

• 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.

  PMID: 34394748 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Tissue, Blood

MeSH Terms

Conditions

Biliary Tract Neoplasms; Cholangiocarcinoma; Gallbladder Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Immunohistochemistry; Base Sequence; Liquid Biopsy

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena; Biopsy; Cytodiagnosis; Specimen Handling

Study Officials

• Hongjae Chon, MD,PhD

  CHA University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2021
• First Posted: May 4, 2021
• Study Start: April 14, 2021
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: August 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)