Locally Advanced Biliary Tract CancersGENTISNCT06893380
Combination Therapy of GCNT and Tislelizumab in Advanced Biliary Tract Cancer
An observational study of Locally Advanced Biliary Tract Cancers and Metastatic Biliary Tract Cancers, run by CHA University at 1 site in South Korea.
Trial summary
This is a multicenter Phase 1b/2 clinical trial investigating the efficacy and safety of a combination regimen of Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab in treatment-naïve patients with unresectable, locally advanced, or metastatic biliary tract cancers (BTC), including intrahepatic… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Locally Advanced Biliary Tract Cancers, Metastatic Biliary Tract Cancers
- What is being tested?
- Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab.
- Type of treatment
- Injection or infusion
- How many people
- 61 participants
- Where
- 1 siteSouth Korea
- Study dates
- 1 Oct 2024to 31 Dec 2026
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with unresectable, locally advanced, or metastatic biliary tract cancer (BTC), including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer, who have not received prior systemic therapy for advanced disease.
Who may be able to join
- Histologically confirmed biliary tract cancer (BTC), including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer (excluding neuroendocrine tumors, sarcoma, mixed cholangiocarcinoma-HCC, and ampullary carcinoma).
- Age ≥ 19 years at the time of signing informed consent.
- Treatment-naïve for unresectable or metastatic BTC, or recurrence/metastasis at least 6 months after curative surgery or adjuvant chemotherapy.
- Measurable lesions per RECIST v1.1.
- ECOG Performance Status (PS) of 0-1 within 14 days prior to the first dose.
- Life expectancy of ≥ 3 months.
Show all 20Show fewer
- Adequate organ function (within 14 days prior to the first dose):
- Hematologic function: Hemoglobin (Hb) ≥ 9.0 g/dL, Absolute neutrophil count (ANC) ≥ 1,500/μL, Platelet count ≥ 100,000/μL
- Renal function: Serum creatinine ≤ 1.5 × ULN or CrCl (Cockcroft-Gault) ≥ 45 mL/min
- Hepatic function: AST and ALT ≤ 3.0 × ULN (≤ 5.0 × ULN for hepatic metastases), Total bilirubin ≤ 1.5 × ULN
- Coagulation: INR ≤ 1.5 or prothrombin time ≤ 1.5 × ULN, aPTT ≤ 1.5 × ULN
- Reproductive status:
- Female participants must provide proof of non-childbearing status or a negative serum pregnancy test within 7 days before the first dose.
- Female subjects receiving cisplatin must agree to effective contraception for 14 months after the last dose; male subjects must agree for 11 months.
- Women of childbearing potential and non-sterilized men must use at least two effective contraceptive methods during the study and for 6 months after the last dose.
- Cardiac function:
- Left ventricular ejection fraction (LVEF) ≥ 50% (by echocardiography or MUGA scan)
- No serious valvular disorders or arrhythmias
- Corrected QT interval ≤ 470 msec at screening
- Willingness to provide tumor tissue samples by biopsy (endoscopic or excisional).
Who cannot join
- Prior treatment history:
- Prior systemic chemotherapy, biological therapy, immunotherapy, or hormone therapy for unresectable or metastatic BTC
- Prior adjuvant chemotherapy or radiation therapy within 6 months before recurrence
- History of another malignancy within 5 years, except:
- Completely resected basal cell carcinoma, stage 1 squamous cell carcinoma, carcinoma in situ, or superficial bladder cancer
- Unresolved toxicities from prior treatment that could affect study evaluation
Show all 38Show fewer
- Known hypersensitivity to any study drug (tislelizumab, gemcitabine, cisplatin, nab-paclitaxel)
- Active or history of autoimmune disease, except:
- Hypothyroidism (on stable hormone therapy), vitiligo, or psoriasis not requiring treatment
- History of interstitial lung disease, pulmonary fibrosis, or radiation pneumonitis
- Active gastrointestinal disease:
- Active peptic ulcer, colitis, or diverticulitis Known central nervous system (CNS) metastasis
- Uncontrolled tumor-related complications: Pericardial effusion, pleural effusion, or ascites requiring intervention, Uncontrolled tumor-related pain
- Significant cardiovascular conditions:
- Myocardial infarction within 180 days before enrollment
- Uncontrolled angina within 180 days before enrollment
- NYHA Class III or IV congestive heart failure
- Persistent hypertension ≥ 150/90 mmHg despite treatment
- Arrhythmias requiring medical intervention
- Thrombosis or vascular diseases requiring surgery
- Uncontrolled diabetes mellitus
- Active infections requiring systemic treatment within 14 days before the first dose
- Recent treatment history:
- Systemic corticosteroids (except prophylactic or short-term use) or immunosuppressants within 28 days before the first dose
- Antitumor therapy (cytotoxic, targeted, or immunotherapy) within 28 days before the first dose
- Pleurodesis within 28 days before the first dose
- Major surgery under general anesthesia within 28 days before the first dose
- Local anesthesia or minor surgery within 14 days before the first dose
- Radiation therapy within 28 days before the first dose (bone metastasis radiation within 14 days is allowed)
- Positive for:
- HIV-1 or HIV-2
- Active Hepatitis B or C (except HBV DNA <500 IU/mL with stable antiviral therapy)
- Pregnant or breastfeeding women
- Use of unapproved drugs within 28 days before enrollment
- Cognitive impairment preventing informed consent
- Severe neuropathy (Grade ≥ 2, CTCAE v5.0)
- Hearing impairment
- Inability or unwillingness to provide informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site, 1 recruiting
- Recruiting
CHA Bundang Medical Center
Seongnam-si, Gyeonggi-do, 13496
Hong Jae Chon, MD. PhD, 82-31-780-3430, minidoctor@cha.ac.kr
Hong Jae Chon
About this study
Official title: A Multicenter Phase 1b/2 Trial Investigating the Efficacy and Toxicity of the Combination of Gemcitabine, Cisplatin, Nab-Paclitaxel, and Tislelizumab in Treatment Naïve Patients With Unresectable, Locally Advanced, or Metastatic BTC
This is a multicenter Phase 1b/2 clinical trial investigating the efficacy and safety of a combination regimen of Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab in treatment-naïve patients with unresectable, locally advanced, or metastatic biliary tract cancers (BTC), including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.
The Phase 1b portion aims to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of Nab-paclitaxel in combination with Gemcitabine, Cisplatin, and Tislelizumab. In the Phase 2 portion, the study will evaluate the Objective Response Rate (ORR) as the primary endpoint, with additional assessments of Overall Survival (OS), Progression-Free Survival (PFS), Disease Control Rate (DCR), and Quality of Life (QoL). Safety and tolerability will also be closely monitored.
This study seeks to leverage the stromal-disrupting effect of Nab-paclitaxel and the immune checkpoint blockade effect of Tislelizumab, combined with the established chemotherapy backbone of Gemcitabine and Cisplatin, to enhance treatment outcomes for BTC patients. The study will enroll patients across three medical centers in South Korea, including CHA Bundang Medical Center, Haeundae Paik Hospital, and Seoul National University Bundang Hospital.
Read the detailed description
Biliary tract cancer (BTC) is a heterogeneous group of malignancies arising from the biliary epithelium, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. Most patients are diagnosed at unresectable, locally advanced, or metastatic stages, and the prognosis remains poor despite advances in systemic therapy.
Since the ABC-02 trial established Gemcitabine plus Cisplatin as the standard first-line chemotherapy for advanced BTC, numerous combination strategies have been explored to improve survival outcomes. In particular, the addition of Nab-paclitaxel to Gemcitabine and Cisplatin has shown promising efficacy by enhancing stromal penetration and drug delivery, supported by preclinical and early clinical studies.
More recently, immune checkpoint inhibitors (ICIs) have emerged as a new treatment option for BTC. The TOPAZ-1 trial demonstrated that adding Durvalumab to Gemcitabine and Cisplatin significantly improved Overall Survival (OS), establishing immunotherapy-based combination therapy as a new standard of care for advanced BTC. Similarly, the KEYNOTE-966 trial confirmed the benefit of Pembrolizumab combined with Gemcitabine and Cisplatin, further supporting the role of ICIs in BTC management.
Tislelizumab, a humanized PD-1 monoclonal antibody, has shown efficacy in various solid tumors and is now being evaluated in BTC. Compared to other PD-1 inhibitors, Tislelizumab was designed to minimize Fc receptor binding, potentially reducing off-target immune activation and enhancing anti-tumor immune response. Combining Tislelizumab with cytotoxic chemotherapy, including Nab-paclitaxel, may offer synergistic benefits by enhancing antigen release and promoting immune response within the tumor microenvironment.
This Phase 1b/2 multicenter trial aims to investigate the safety, tolerability, and efficacy of the combination regimen of Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab in treatment-naïve patients with unresectable, locally advanced, or metastatic BTC. The study will be conducted across three medical centers in South Korea: CHA Bundang Medical Center, Haeundae Paik Hospital, and Seoul National University Bundang Hospital.
The Phase 1b part will determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Nab-paclitaxel when combined with Gemcitabine, Cisplatin, and Tislelizumab. Dose escalation will follow a standard 3+3 design, with dose-limiting toxicities (DLTs) assessed during Cycle 1.
In the Phase 2 part, the primary endpoint will be Objective Response Rate (ORR), with secondary endpoints including Overall Survival (OS), Progression-Free Survival (PFS), Disease Control Rate (DCR), Duration of Response (DOR), and Quality of Life (QoL) assessed using EORTC QLQ-C30 and QLQ-BIL21. Safety and tolerability will also be evaluated throughout the study.
This study seeks to optimize the therapeutic potential of chemotherapy plus immunotherapy by incorporating Nab-paclitaxel at a reduced dose to enhance tolerability while maintaining efficacy. Exploratory objectives include assessing immunological and metabolic changes induced by the study drugs, as well as collecting tumor and blood samples for future biomarker analyses.
Through this trial, we aim to establish a novel first-line treatment strategy for advanced BTC, potentially improving survival outcomes beyond the current standard of care.
- Being tested
- Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab.
- Medical subject headings
- Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab.Drug
Tislelizumab: IV 200mg on Day 1 of every 3-week cycle Nab-paclitaxel: IV 75mg/m2 on Days 1 and 8 of every 3-week cycle (up to 16 cycles) Gemcitabine: IV 800mg/m2 on Days 1 and 8 of every 3-week cycle Cisplatin: IV 25mg/m2 on Days 1 and 8 of every 3-week cycle (up to 8 cycles)
| Study group | Role | What they receive |
|---|---|---|
| Combination Therapy Group | This group consists of patients with unresectable, locally advanced, or metastatic biliary tract cancer who will receive combination therapy with Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab. Receives: Drug: Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
The proportion of patients who achieve a complete response (CR) or partial response (PR) according to RECIST v1.1.
Measured: Up to 24 months after treatment initiation.
Secondary outcomes (7)
Overall Survival (OS)
Time from the date of first dose to the date of death from any cause.
Measured: Up to 36 months after treatment initiation.
Progression-Free Survival (PFS)
Time from the date of first dose to disease progression per RECIST v1.1 or death from any cause.
Measured: Up to 24 months after treatment initiation.
Disease Control Rate (DCR)
The proportion of patients who achieve complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1.
Measured: Up to 24 months after treatment initiation.
Duration of Response (DOR)
Time from first documented response (CR or PR) to progression or death.
Measured: Up to 24 months after treatment initiation.
Quality of Life (QoL)- EORTC QLQ-C30
Patient-reported quality of life assessed using the EORTC QLQ-C30 questionnaire.
Measured: Up to 24 months after treatment initiation.
Quality of Life (QoL)- EORTC QLQ-BIL21
Patient-reported quality of life assessed using the EORTC QLQ-BIL21 questionnaire.
Measured: Up to 24 months after treatment initiation.
Safety and Tolerability
Incidence, severity, and type of adverse events (AEs), graded per NCI CTCAE v5.0.
Measured: Up to 30 days after last dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2025
- Study start1 Oct 2024
- Primary completion8 May 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Biliary Tract CancersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 61 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- CHA University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hong Jae Chon, CHA University
- Investigators
- Hong Jae Chon, MD. PhD, Principal investigator, Principal Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06893380
- Sponsor's protocol ID
- CHAMC 2024-09-029
- Acronym
- GENTIS
- Status last verified
- Sep 2025
- First submitted
- 12 Mar 2025
- Last updated
- 15 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sirica AE, Gores GJ. Desmoplastic stroma and cholangiocarcinoma: clinical implications and therapeutic targeting. Hepatology. 2014 Jun;59(6):2397-402. doi: 10.1002/hep.26762. Epub 2014 Apr 9. No abstract available.
PubMed 24123296Coulouarn C, Clement B. Stellate cells and the development of liver cancer: therapeutic potential of targeting the stroma. J Hepatol. 2014 Jun;60(6):1306-9. doi: 10.1016/j.jhep.2014.02.003. Epub 2014 Feb 12.
PubMed 24530649Claperon A, Mergey M, Aoudjehane L, Ho-Bouldoires TH, Wendum D, Prignon A, Merabtene F, Firrincieli D, Desbois-Mouthon C, Scatton O, Conti F, Housset C, Fouassier L. Hepatic myofibroblasts promote the progression of human cholangiocarcinoma through activation of epidermal growth factor receptor. Hepatology. 2013 Dec;58(6):2001-11. doi: 10.1002/hep.26585. Epub 2013 Oct 25.
PubMed 23787814Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klumpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853-1865. doi: 10.1016/S0140-6736(23)00727-4. Epub 2023 Apr 16.
PubMed 37075781Oh DY, Ruth He A, Qin S, Chen LT, Okusaka T, Vogel A, Kim JW, Suksombooncharoen T, Ah Lee M, Kitano M, Burris H, Bouattour M, Tanasanvimon S, McNamara MG, Zaucha R, Avallone A, Tan B, Cundom J, Lee CK, Takahashi H, Ikeda M, Chen JS, Wang J, Makowsky M, Rokutanda N, He P, Kurland JF, Cohen G, Valle JW. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evid. 2022 Aug;1(8):EVIDoa2200015. doi: 10.1056/EVIDoa2200015. Epub 2022 Jun 1.
PubMed 38319896Piha-Paul SA, Oh DY, Ueno M, Malka D, Chung HC, Nagrial A, Kelley RK, Ros W, Italiano A, Nakagawa K, Rugo HS, de Braud F, Varga AI, Hansen A, Wang H, Krishnan S, Norwood KG, Doi T. Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies. Int J Cancer. 2020 Oct 15;147(8):2190-2198. doi: 10.1002/ijc.33013. Epub 2020 May 2.
PubMed 32359091Kim RD, Chung V, Alese OB, El-Rayes BF, Li D, Al-Toubah TE, Schell MJ, Zhou JM, Mahipal A, Kim BH, Kim DW. A Phase 2 Multi-institutional Study of Nivolumab for Patients With Advanced Refractory Biliary Tract Cancer. JAMA Oncol. 2020 Jun 1;6(6):888-894. doi: 10.1001/jamaoncol.2020.0930.
PubMed 32352498Shroff RT, King G, Colby S, Scott AJ, Borad MJ, Goff L, Matin K, Mahipal A, Kalyan A, Javle MM, El Dika I, Tan B, Cheema P, Patel A, Iyer R, Kelley RK, Thumar J, El-Khoueiry A, Guthrie KA, Chiorean EG, Hochster H, Philip PA. SWOG S1815: A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers. J Clin Oncol. 2025 Feb 10;43(5):536-544. doi: 10.1200/JCO-24-01383. Epub 2024 Dec 13.
PubMed 39671534Shroff 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.
PubMed 30998813Valle 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.
PubMed 20375404
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase 1b/2 Trial Investigating the Efficacy and Toxicity of the Combination of Gemcitabine, Cisplatin, Nab-Paclitaxel, and Tislelizumab in Treatment Naïve Patients With Unresectable, Locally Advanced, or Metastatic BTC
- ClinicalTrials.gov ID
- NCT06893380
- Acronym / sponsor ID
- GENTIS / CHAMC 2024-09-029
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 61 participants (estimated)
- Lead sponsor
- CHA UniversityUniversity, hospital or other
- Study start
- 1 Oct 2024 (actual)
- Primary completion
- 8 May 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 25 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter Phase 1b/2 clinical trial investigating the efficacy and safety of a combination regimen of Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab in treatment-naïve patients with unresectable, locally advanced, or metastatic biliary tract cancers (BTC), including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.
The Phase 1b portion aims to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of Nab-paclitaxel in combination with Gemcitabine, Cisplatin, and Tislelizumab. In the Phase 2 portion, the study will evaluate the Objective Response Rate (ORR) as the primary endpoint, with additional assessments of Overall Survival (OS), Progression-Free Survival (PFS), Disease Control Rate (DCR), and Quality of Life (QoL). Safety and tolerability will also be closely monitored.
This study seeks to leverage the stromal-disrupting effect of Nab-paclitaxel and the immune checkpoint blockade effect of Tislelizumab, combined with the established chemotherapy backbone of Gemcitabine and Cisplatin, to enhance treatment outcomes for BTC patients. The study will enroll patients across three medical centers in South Korea, including CHA Bundang Medical Center, Haeundae Paik Hospital, and Seoul National University Bundang Hospital.
Detailed description
Biliary tract cancer (BTC) is a heterogeneous group of malignancies arising from the biliary epithelium, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. Most patients are diagnosed at unresectable, locally advanced, or metastatic stages, and the prognosis remains poor despite advances in systemic therapy.
Since the ABC-02 trial established Gemcitabine plus Cisplatin as the standard first-line chemotherapy for advanced BTC, numerous combination strategies have been explored to improve survival outcomes. In particular, the addition of Nab-paclitaxel to Gemcitabine and Cisplatin has shown promising efficacy by enhancing stromal penetration and drug delivery, supported by preclinical and early clinical studies.
More recently, immune checkpoint inhibitors (ICIs) have emerged as a new treatment option for BTC. The TOPAZ-1 trial demonstrated that adding Durvalumab to Gemcitabine and Cisplatin significantly improved Overall Survival (OS), establishing immunotherapy-based combination therapy as a new standard of care for advanced BTC. Similarly, the KEYNOTE-966 trial confirmed the benefit of Pembrolizumab combined with Gemcitabine and Cisplatin, further supporting the role of ICIs in BTC management.
Tislelizumab, a humanized PD-1 monoclonal antibody, has shown efficacy in various solid tumors and is now being evaluated in BTC. Compared to other PD-1 inhibitors, Tislelizumab was designed to minimize Fc receptor binding, potentially reducing off-target immune activation and enhancing anti-tumor immune response. Combining Tislelizumab with cytotoxic chemotherapy, including Nab-paclitaxel, may offer synergistic benefits by enhancing antigen release and promoting immune response within the tumor microenvironment.
This Phase 1b/2 multicenter trial aims to investigate the safety, tolerability, and efficacy of the combination regimen of Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab in treatment-naïve patients with unresectable, locally advanced, or metastatic BTC. The study will be conducted across three medical centers in South Korea: CHA Bundang Medical Center, Haeundae Paik Hospital, and Seoul National University Bundang Hospital.
The Phase 1b part will determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Nab-paclitaxel when combined with Gemcitabine, Cisplatin, and Tislelizumab. Dose escalation will follow a standard 3+3 design, with dose-limiting toxicities (DLTs) assessed during Cycle 1.
In the Phase 2 part, the primary endpoint will be Objective Response Rate (ORR), with secondary endpoints including Overall Survival (OS), Progression-Free Survival (PFS), Disease Control Rate (DCR), Duration of Response (DOR), and Quality of Life (QoL) assessed using EORTC QLQ-C30 and QLQ-BIL21. Safety and tolerability will also be evaluated throughout the study.
This study seeks to optimize the therapeutic potential of chemotherapy plus immunotherapy by incorporating Nab-paclitaxel at a reduced dose to enhance tolerability while maintaining efficacy. Exploratory objectives include assessing immunological and metabolic changes induced by the study drugs, as well as collecting tumor and blood samples for future biomarker analyses.
Through this trial, we aim to establish a novel first-line treatment strategy for advanced BTC, potentially improving survival outcomes beyond the current standard of care.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination Therapy Group | – | Drug: Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab.This group consists of patients with unresectable, locally advanced, or metastatic biliary tract cancer who will receive combination therapy with Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with unresectable, locally advanced, or metastatic biliary tract cancer (BTC), including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer, who have not received prior systemic therapy for advanced disease.
Key inclusion criteria (20 listed)
- Histologically confirmed biliary tract cancer (BTC), including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer (excluding neuroendocrine tumors, sarcoma, mixed cholangiocarcinoma-HCC, and ampullary carcinoma).
- Age ≥ 19 years at the time of signing informed consent.
- Treatment-naïve for unresectable or metastatic BTC, or recurrence/metastasis at least 6 months after curative surgery or adjuvant chemotherapy.
- Measurable lesions per RECIST v1.1.
- ECOG Performance Status (PS) of 0-1 within 14 days prior to the first dose.
Key exclusion criteria (38 listed)
- Prior treatment history:
- History of another malignancy within 5 years, except:
- Unresolved toxicities from prior treatment that could affect study evaluation
- Known hypersensitivity to any study drug (tislelizumab, gemcitabine, cisplatin, nab-paclitaxel)
- Active or history of autoimmune disease, except:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab.Tislelizumab: IV 200mg on Day 1 of every 3-week cycle Nab-paclitaxel: IV 75mg/m2 on Days 1 and 8 of every 3-week cycle (up to 16 cycles) Gemcitabine: IV 800mg/m2 on Days 1 and 8 of every 3-week cycle Cisplatin: IV 25mg/m2 on Days 1 and 8 of every 3-week cycle (up to 8 cycles) | Drug | Combination Therapy Group |
Primary outcome
Objective Response Rate (ORR)
Time frame: Up to 24 months after treatment initiation.
The proportion of patients who achieve a complete response (CR) or partial response (PR) according to RECIST v1.1.
7 secondary outcomes
Overall Survival (OS)
Time frame: Up to 36 months after treatment initiation.
Progression-Free Survival (PFS)
Time frame: Up to 24 months after treatment initiation.
Disease Control Rate (DCR)
Time frame: Up to 24 months after treatment initiation.
Duration of Response (DOR)
Time frame: Up to 24 months after treatment initiation.
Quality of Life (QoL)- EORTC QLQ-C30
Time frame: Up to 24 months after treatment initiation.
Quality of Life (QoL)- EORTC QLQ-BIL21
Time frame: Up to 24 months after treatment initiation.
Safety and Tolerability
Time frame: Up to 30 days after last dose.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2025.
- Background: PubMed 24123296Sirica AE, Gores GJ. Desmoplastic stroma and cholangiocarcinoma: clinical implications and therapeutic targeting. Hepatology. 2014 Jun;59(6):2397-402. doi: 10.1002/hep.26762. Epub 2014 Apr 9. No abstract available.
- Background: PubMed 24530649Coulouarn C, Clement B. Stellate cells and the development of liver cancer: therapeutic potential of targeting the stroma. J Hepatol. 2014 Jun;60(6):1306-9. doi: 10.1016/j.jhep.2014.02.003. Epub 2014 Feb 12.
- Background: PubMed 23787814Claperon A, Mergey M, Aoudjehane L, Ho-Bouldoires TH, Wendum D, Prignon A, Merabtene F, Firrincieli D, Desbois-Mouthon C, Scatton O, Conti F, Housset C, Fouassier L. Hepatic myofibroblasts promote the progression of human cholangiocarcinoma through activation of epidermal growth factor receptor. Hepatology. 2013 Dec;58(6):2001-11. doi: 10.1002/hep.26585. Epub 2013 Oct 25.
- Background: PubMed 37075781Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klumpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853-1865. doi: 10.1016/S0140-6736(23)00727-4. Epub 2023 Apr 16.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Hong Jae Chon, MD. PhD principal investigator
Principal Investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Locally Advanced Biliary Tract Cancers and Metastatic Biliary Tract Cancers, run by CHA University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hong Jae Chon, MD. PhD (82-31-780-3928, minidoctor@cha.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Up to 24 months after treatment initiation.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06893380, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2025.