Combination Therapy of GCNT and Tislelizumab in Advanced Biliary Tract Cancer
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age19+
SponsorCHA University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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
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
Trial 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.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab.
DrugTislelizumab: 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)
Treatment groups
61 Participants
are divided into 1 treatment groupGroup A: Combination Therapy Group1 intervention
Trial outcomes
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.
Time frame
Up to 24 months after treatment initiation.Secondary outcomes
1
Overall Survival (OS)
Time from the date of first dose to the date of death from any cause.
Time frame
Up to 36 months after treatment initiation.2
Progression-Free Survival (PFS)
Time from the date of first dose to disease progression per RECIST v1.1 or death from any cause.
Time frame
Up to 24 months after treatment initiation.3
Disease Control Rate (DCR)
The proportion of patients who achieve complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1.
Time frame
Up to 24 months after treatment initiation.4
Duration of Response (DOR)
Time from first documented response (CR or PR) to progression or death.
Time frame
Up to 24 months after treatment initiation.Other outcomes
1
Immune System Response and Immunomodulation Markers
Changes in immune system markers in peripheral blood and tumor tissue samples, including: CD8+ T-cell count (%) PD-L1 expression levels in tumor tissues Cytokine levels (e.g., IFN-γ, IL-6, TNF-α) T-cell receptor (TCR) clonality
Time frame
Baseline, during treatment (every 3 cycles; each cycle = 21 days), and at progression (up to 24 months)2
Metabolic Biomarker Changes in Peripheral Blood and Tumor Tissues
Changes in metabolic biomarkers in peripheral blood and tumor tissue samples, including: Serum glucose levels (mg/dL) and insulin resistance markers (e.g., HOMA-IR) Lipid metabolism markers (e.g., triglycerides, total cholesterol, LDL, HDL) Lactate and pyruvate levels as indicators of altered tumor metabolism Amino acid profiling (e.g., glutamine, alanine) for metabolic reprogramming
Time frame
Baseline, during treatment, and at progression (up to 24 months)3
Collection and Storage of DNA and RNA for Future Exploratory Study
To collect and store DNA and RNA (following ethical guidelines) for future exploratory research investigating genetic variations that may affect responses to study treatment (distribution, safety, tolerability, and efficacy) and/or susceptibility to diseases. Participation in this exploratory study is optional.
Time frame
Baseline and during treatment (up to 24 months)4
Quality of Life (QoL) - EORTC QLQ-C30
Patient-reported quality of life assessed using the EORTC QLQ-C30 questionnaire, which evaluates physical, emotional, cognitive, and social functioning.
Time frame
Baseline, every 3 cycles during treatment (each cycle = 21 days), and at the end of treatment (up to 24 months)Sponsors and contacts
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Source ClinicalTrials.gov