Biomarker Discovery in Patients With Advanced Biliary Tract Cancer

Study Overview
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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).

Official Title
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Discovery of Molecular Biomarkers for Predicting Response Through RNA Sequencing in Patients With Advanced Biliary Tract Cancer Who Received Nab-paclitaxel Plus Gemcitabine-cisplatin

Conditions
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Biliary Tract Cancer, Cholangiocarcinoma, Gallbladder Cancer

Intervention / Treatment
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* Drug: nab-paclitaxel plus gemcitabine-cisplatin


Participation Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Gem/Cis/nab-P<br>Gemcitabine + Cisplatin + Nab-Paciltaxel | Drug: nab-paclitaxel plus gemcitabine-cisplatin<br>* - gemcitabine 800mg/m2 + cisplatin 25 mg/m2 + nab-paclitaxel 100mg/m2 on day 1 and day 8, every 21 days<br>* Other names: immunohistochemistry, NGS, RNA-sequencing, Liquid biopsy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multi-omics analysis | Multi-omics analysis to further subtype and find therapeutic targets of biliary tract cancer | 2 years | 
| Biomarkers on the efficacy of Gemcitabine/Cisplatin/Nab-paclitaxel for advanced biliary tract cancer | Molecular biomarker associated with overall survival, progression-free survival and objective response rate in patients who receive Gemcitabine/Cisplatin/Nab-paclitaxel chemotherapy | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biliary Tract cancer, Gemcitabine, Cisplatin, nab-paclitaxel, RNA sequencing, biomarker