Clinical Feasibility of Nab-paclitaxel Plus Gemcitabine-cisplatin Chemotherapy in Locally Advanced Cholangiocarcinoma

Study Overview
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Brief Summary
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The objective of this observational study is to identify patients with locally advanced cholangiocarcinoma treated with nab-paclitaxel and gemcitabine-cisplatin chemotherapy. In this clinical study, peripheral blood and tumor tissues will be analyzed at baseline and every 3 cycles after systemic drug treatment in patients with locally advanced cholangiocarcinoma, and correlation with treatment was analyzed. This is an exploratory study to discover biomarkers that are highly correlated with treatment response.

Detailed Description
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Although surgical treatment is the only treatment for cholangiocarcinoma, most patients are diagnosed at a metastatic or locally advanced stage, and palliative chemotherapy is the main treatment method for this group of patients. Recently, with the introduction of gemcitabine, cisplatin, and nab-paclitaxel combination chemotherapy for locally advanced cholangiocarcinoma, the treatment response rate is improving, and the number of cases of downgrade to an operable state is increasing. However, there are no prospective studies confirming the rate of conversion surgery after gemcitabine, cisplatin, and Nab-paclitaxel combination therapy in locally advanced cholangiocarcinoma. As a result of long-term follow-up, more than 30% of patients relapsed, so it is urgent to develop predictive biomarkers before surgery. There are reports that tumor DNA (ctDNA) accurately predicts recurrence after surgical treatment. Using blood samples that are relatively easy to collect compared to biopsies, it is possible to quantitatively measure tumor burden and to evaluate the effectiveness of systemic treatments such as chemotherapy. It is a very popular tool for measuring and predicting the success of surgical treatment in advanced solid cancer. The purpose of this study was to determine the rate of conversion surgery after treatment with Gemcitabine, Cisplatin, and Nab-paclitaxel in patients with inoperable locally advanced cholangiocarcinoma through an observational study. In addition, the purpose of this study is to verify the performance of biomarkers in predicting recurrence and survival after ctDNA and RNA conversion surgery in a situation where there is no clinical strategy to select a group of patients who can try radical resection.

Official Title
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Clinical Feasibility of Nab-paclitaxel Plus Gemcitabine-cisplatin Chemotherapy in Patients With Locally Advanced Cholangiocarcinoma and Discovery of Biomarkers

Conditions
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Locally Advanced Cholangiocarcinoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Those above the age of 19 who understand the purpose of the study and agree to participate in the collection of samples during the study. Patients with histologically or cytologically confirmed inoperable locally advanced cholangiocarcinoma (gallbladder cancer, extrahepatic biliary tract cancer, intrahepatic biliary tract cancer) Patients who underwent an NGS test with advanced cholangiocarcinoma tissues Patients planning to be treated with nab-paclitaxel plus gemcitabine-cisplatin combination therapy ECOG performance status 0 or 1 Exclusion Criteria: Systemic condition accompanied by instability of vital signs such as infection or organ failure Patients who have previously received palliative chemotherapy for cholangiocarcinoma Those with mental/neurological conditions or dementia who have difficulties understanding and completing the consent form Those who are assessed as not suitable for this study, at the discretion of the researcher

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 |
| --- | --- |
| nab-paclitaxel plus gemcitabine-cisplatin<br>gemcitabine, 800 mg/m2, cisplatin, 25 mg/m2, and nab-paclitaxel, 100 mg/m2, on days 1 and 8 of 21-day cycles | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conversion Surgery Rate | Proportion of patients who underwent conversion surgery | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall survival is calculated as the time from initiation of treatment until death. The follow-up period is from initiation of treatment until the date of death or for 1 year after last patient enrollment, whichever is earlier. | 2 years | 
| ORR | Overall Response Rate follow-up will be conducted every 6 weeks. Lesion will be evaluated according to RECIST 1.1 (CR, complete disappearance or LN short axis diameter < 1.0cm; PR, ≥30% reduction; PD, ≥20% increase; SD, neither CR, PR nor PD). The follow-up period is from initiation of treatment until date of disease progression or death or for 1 year after last patient enrollment, whichever is earlier. | 1 year | 
| PFS | Progression Free Survival is calculated as the time from initiation of treatment until the date of disease progression or death without PD. The follow-up period is from initiation of treatment until the date of disease progression or death without PD or for 1 year after last patient enrollment, whichever is earlier. Each time ORR is measured at 2-month intervals, progression-free survival will be checked. | 2 years |