NCT06963060

Gem+Nab-P+LEN+TIS for Advanced Unresectable BTC (GALENT-BT)

Xinhua Hospital A Ffiliated to Shanghai Jiaotong University School of Medicine

• Status: Enrolling By Invitation
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 44 (estimated)
• Sponsor: Wei Gong · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

1. 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. 2. 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. 3. 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). 4. 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. 5. 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. 6. 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.

Conditions

• Gallbladder Cancer
• Cholangiocarcinoma

Interventions

Type	Name	Description
DRUG	Gemcitabine nab-PaclitaxelLenvatinibTislelizumab	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.

Timeline

• Start date: 2024-06-01
• Primary completion: 2027-06-30
• Completion: 2027-06-30
• First posted: 2025-05-08
• Last updated: 2025-05-08

Locations

1 site across 1 country: China