Clinical trial NCT04871321: Biomarker Discovery in Patients With Advanced Biliary Tract Cancer
Official title: Discovery of Molecular Biomarkers for Predicting Response Through RNA Sequencing in Patients With Advanced Biliary Tract Cancer Who Received Nab-paclitaxel Plus Gemcitabine-cisplatin
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Biliary Tract Cancer
Cholangiocarcinoma
Gallbladder Cancer
Keywords: Biliary Tract cancer
Gemcitabine
Cisplatin
nab-paclitaxel
RNA sequencing
biomarker
Lead sponsor: CHA University
Sponsor class: OTHER
Collaborators: name: Dong-A Pharmaceutical
First posted: 2021-05-04
Enrollment: 120
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with advanced biliary tract cancer will be recruited at CHA Bundang Medical Center

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).

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 0-1.
* 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.

Primary outcomes:
measure: collected tumor samples
timeFrame: through study completion, an average of 2 years
measure: collected blood samples
timeFrame: through study completion, an average of 2 years
Secondary outcomes:
measure: Multi-omics analysis
timeFrame: 2 years
measure: Biomarkers on the efficacy of Gemcitabine/Cisplatin/Nab-paclitaxel for advanced biliary tract cancer
timeFrame: 2 years
Other outcomes:
Locations:
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Center
state: Gyeonggi-do
Study officials:
affiliation: CHA University
name: Hongjae Chon, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
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