Discovery of Molecular Biomarkers for Predicting Response Through RNA Sequencing in Patients With Advanced Biliary Tract Cancer Who Received Nab-paclitaxel Plus Gemcitabine-cisplatin
Overview
- Phase
- Not Applicable
- Intervention
- nab-paclitaxel plus gemcitabine-cisplatin
- Conditions
- Biliary Tract Cancer
- Sponsor
- CHA University
- Enrollment
- 119
- Locations
- 1
- Primary Endpoint
- collected tumor samples
- Status
- Completed
- Last Updated
- 8 months ago
Overview
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.
Detailed Description
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).
Investigators
Eligibility Criteria
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-
- •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.
Arms & Interventions
Gem/Cis/nab-P
Gemcitabine + Cisplatin + Nab-Paciltaxel
Intervention: nab-paclitaxel plus gemcitabine-cisplatin
Outcomes
Primary Outcomes
collected tumor samples
Time Frame: through study completion, an average of 2 years
tumor samples from patients with hepatobiliary cancers (incidence of genetic alteration, association with treatment response and survival duration)
collected blood samples
Time Frame: through study completion, an average of 2 years
blood samples from patients with hepatobiliary cancers (incidence of genetic alteration, association with treatment response and survival duration)
Secondary Outcomes
- Multi-omics analysis(2 years)
- Biomarkers on the efficacy of Gemcitabine/Cisplatin/Nab-paclitaxel for advanced biliary tract cancer(2 years)