Combination Therapy of GCNT and Tislelizumab in Advanced Biliary Tract Cancer

NCT06893380 | Recruiting

• 1 other identifier: CHAMC 2024-09-029
• Study Type: observational
• Target: 61
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Locally Advanced Biliary Tract Cancers; Metastatic Biliary Tract Cancers

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The proportion of patients who achieve a complete response (CR) or partial response (PR) according to RECIST v1.1.

  Up to 24 months after treatment initiation.

Secondary Outcomes (7)

• Overall Survival (OS)

  Up to 36 months after treatment initiation.

• Progression-Free Survival (PFS)

  Up to 24 months after treatment initiation.

• Disease Control Rate (DCR)

  Up to 24 months after treatment initiation.

• Duration of Response (DOR)

  Up to 24 months after treatment initiation.

• Quality of Life (QoL)- EORTC QLQ-C30

  Up to 24 months after treatment initiation.

Other Outcomes (5)

• Immune System Response and Immunomodulation Markers

  Baseline, during treatment (every 3 cycles; each cycle = 21 days), and at progression (up to 24 months)

• Metabolic Biomarker Changes in Peripheral Blood and Tumor Tissues

  Baseline, during treatment, and at progression (up to 24 months)

• Collection and Storage of DNA and RNA for Future Exploratory Study

  Baseline and during treatment (up to 24 months)

Study Arms (1)

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.

Drug: Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab.

Interventions

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)

Combination Therapy Group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• CHA University: lead

Study Sites (1)

CHA Bundang Medical Center

Seongnam-si, Gyeonggi-do, 13496, South Korea

RECRUITING

Related Publications (10)

• 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.

  PMID: 24123296 BACKGROUND

• Coulouarn 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.

  PMID: 24530649 BACKGROUND

• Claperon 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.

  PMID: 23787814 BACKGROUND

• Kelley 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.

  PMID: 37075781 BACKGROUND

• Oh 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.

  PMID: 38319896 BACKGROUND

• Piha-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.

  PMID: 32359091 BACKGROUND

• Kim 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.

  PMID: 32352498 BACKGROUND

• Shroff 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.

  PMID: 39671534 BACKGROUND

• 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.

  PMID: 30998813 BACKGROUND

• 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.

  PMID: 20375404 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Tumor tissue and blood samples will be collected and stored for future biomarker analysis, including DNA and RNA extraction.

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Gemcitabine; Cisplatin; 130-nm albumin-bound paclitaxel; tislelizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Hong Jae Chon, MD. PhD

  Principal Investigator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hong Jae Chon, MD. PhD

CONTACT

82-31-780-3928; minidoctor@cha.ac.kr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 12, 2025
• First Posted: March 25, 2025
• Study Start: October 1, 2024
• Primary Completion: May 8, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)