Clinical trial NCT05677217: Clinical Feasibility of Nab-paclitaxel Plus Gemcitabine-cisplatin Chemotherapy in Locally Advanced Cholangiocarcinoma
Official title: Clinical Feasibility of Nab-paclitaxel Plus Gemcitabine-cisplatin Chemotherapy in Patients With Locally Advanced Cholangiocarcinoma and Discovery of Biomarkers
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Locally Advanced Cholangiocarcinoma
Lead sponsor: CHA University
Sponsor class: OTHER
First posted: 2023-01-10
Enrollment: 100
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: Recruitment of advanced cholangiocarcinoma patients through a competitive registration process at CHA Bundang Hospital, Haeundae Paik Hospital, and Seoul National University Bundang Hospital.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Conversion Surgery Rate
timeFrame: 6 months
Secondary outcomes:
measure: OS
timeFrame: 2 years
measure: ORR
timeFrame: 1 year
measure: PFS
timeFrame: 2 years
Other outcomes:
measure: Recurrence Rate
timeFrame: through study completion, an average of 1 year
measure: Change of ctDNA
timeFrame: From baseline to 1 year of treatment
measure: Identification of potential Biomarkers of Conversion Surgery
timeFrame: From baseline to 1 year of treatment
Locations:
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Center
state: Gyeonggi-do
Study officials:
affiliation: CHA Bundang Medical Center
name: Hong Jae Chon, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Tie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S, Wong R, Shapiro J, Lee M, Harris S, Khattak A, Burge M, Harris M, Lynam J, Nott L, Day F, Hayes T, McLachlan SA, Lee B, Ptak J, Silliman N, Dobbyn L, Popoli M, Hruban R, Lennon AM, Papadopoulos N, Kinzler KW, Vogelstein B, Tomasetti C, Gibbs P; DYNAMIC Investigators. Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer. N Engl J Med. 2022 Jun 16;386(24):2261-2272. doi: 10.1056/NEJMoa2200075. Epub 2022 Jun 4.
citation: Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M, Kosmider S, Skinner I, Wong R, Steel M, Tran B, Desai J, Jones I, Haydon A, Hayes T, Price TJ, Strausberg RL, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016 Jul 6;8(346):346ra92. doi: 10.1126/scitranslmed.aaf6219.
citation: 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.