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The goal of this clinical trial is to evaluate the efficacy and safety of combining Gemcitabine, nab-Paclitaxel, Lenvatinib, and Tislelizumab in adults aged 18-75 years with advanced unresectable biliary tract malignancies (including gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma). The main questions it aims to answer are:
What is the objective response rate (ORR) of this quadruplet regimen as first-line therapy?
What are the secondary outcomes, including disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety profile?
This is a single-arm, open-label, phase II study with no comparison group.
Participants will:
Receive Gemcitabine (1000 mg/m² IV on Days 1 and 8) and nab-Paclitaxel (125 mg/m² IV on Days 1 and 8) every 3 weeks.
Take Lenvatinib (4-8 mg orally daily on Days 1-21).
Receive Tislelizumab (200 mg IV on Day 1) every 3 weeks.
Undergo 6-8 treatment cycles (adjusted for tolerability) with regular imaging, laboratory tests, and safety assessments.
Be followed for 3 years to monitor survival and long-term outcomes.
The study plans to enroll 29 participants and will be conducted at a single center over 36 months.
Full description
Study Background Biliary tract malignancies (BTCs), including gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC), are aggressive cancers with a 5-year survival rate <5%. Current first-line systemic therapies (e.g., gemcitabine/cisplatin) yield limited efficacy (ORR <30%, median OS ~11.7 months). Preclinical and clinical evidence suggests synergistic effects of combining chemotherapy, anti-angiogenic agents, and immune checkpoint inhibitors. The GALENT-BT trial evaluates a novel quadruplet regimen-Gemcitabine + nab-Paclitaxel + Lenvatinib + Tislelizumab-to improve outcomes in advanced unresectable BTCs.
Study Objectives
Primary Objective: Assess the safety and tolerability of the quadruplet regimen over 8 treatment cycles.
Secondary Objectives:
Evaluate objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and surgical conversion rate.
Monitor adverse events (AEs), serious adverse events (SAEs), and quality of life (QoL).
Exploratory Objectives: Investigate biomarkers (e.g., PD-L1 expression, genetic mutations) and radiomic/pathologic features associated with treatment response.
Study Design
Design: Prospective, single-arm, open-label, single-center, phase II trial.
Sample Size: Two-stage enrollment:
Stage 1 (Lead-in): 9 participants for initial safety evaluation. If ≤3/9 experience grade ≥3 AEs, proceed to Stage 2.
Stage 2 (Expansion): 20 additional participants (total 29 evaluable patients).
Duration: 36 months (June 2024-June 2027).
Study Population
Inclusion Criteria:
Adults aged 18-75 years with histologically confirmed, untreated, advanced unresectable BTC (GBC/ICC/ECC) or recurrent BTC (≥3 months post-adjuvant therapy).
ECOG PS 0-1, measurable disease per RECIST 1.1, adequate organ function.
Exclusion Criteria: Prior systemic therapy for advanced BTC, severe comorbidities, pregnancy, or intolerance to study drugs.
Intervention
Regimen:
Gemcitabine: 1000 mg/m² IV on Days 1 and 8 of each 21-day cycle.
nab-Paclitaxel: 125 mg/m² IV on Days 1 and 8.
Lenvatinib: 4-8 mg orally daily (weight-based dosing) on Days 1-21.
Tislelizumab: 200 mg IV on Day 1.
Treatment Duration: 6-8 cycles (adjustable for tolerability), followed by 3-year survival follow-up.
Assessments
Efficacy:
Tumor response evaluated by CT/MRI every 6 weeks using RECIST 1.1.
ORR, DCR, PFS, OS, and surgical conversion rate calculated.
Safety:
AEs/SAEs graded per CTCAE v5.0.
Laboratory monitoring (hematology, liver/renal function, thyroid panels).
QoL: Assessed via EORTC QLQ-HCC18 questionnaire at baseline, treatment cycles, and follow-up.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Aged 18-75 years, regardless of gender.
Histologically or cytologically confirmed, untreated primary advanced unresectable biliary tract malignancies (BTC), including intrahepatic cholangiocarcinoma (ICC), extrahepatic chololiocarcinoma (ECC), and gallbladder cancer (GBC); or untreated recurrent BTC (prior adjuvant/neoadjuvant chemotherapy allowed if completed ≥3 months before recurrence, excluding regimens containing PD-1/L1 inhibitors, gemcitabine, nab-paclitaxel, or lenvatinib).
ECOG performance status score 0-1.
Expected survival ≥3 months.
At least one measurable target lesion per RECIST v1.1 criteria.
Adequate organ function:
Hematologic: Hemoglobin ≥90 g/L; WBC ≥lower limit of normal (LLN); ANC ≥1.5×10⁹/L; platelets ≥100×10⁹/L.
Renal: Serum creatinine ≤1.5×ULN; endogenous creatinine clearance rate ≥55 mL/min.
Hepatic: Total bilirubin ≤1.5×ULN; ALT/AST ≤2.5×ULN (≤3×ULN for intrahepatic BTC or liver metastases; ALT/AST ≤5×ULN for liver metastases).
Coagulation: INR ≤1.5×ULN; APTT within normal range.
No prior systemic therapy for advanced BTC (chemotherapy, radiotherapy, targeted therapy, immunotherapy, or hormonal therapy). Patients with post-R2 resection are eligible.
Negative serum/urine pregnancy test (for women of childbearing potential) and agreement to use contraception during the study and for 6 months post-treatment.
Willing and able to provide written informed consent.
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
44 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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