Xinhua Hospital A Ffiliated to Shanghai Jiaotong University School of Medicine
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- ORR
研究概览
简要总结
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.
详细描述
- 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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •Severe systemic infection or uncontrolled comorbidities (e.g., heart failure, thyroid disorders, psychiatric conditions).
- •Known hypersensitivity or intolerance to study drugs or their excipients.
- •Pregnancy, lactation, or refusal to use effective contraception.
- •Participation in other clinical trials within 30 days prior to enrollment.
- •Inability to understand or unwillingness to sign informed consent.
- •Any condition that, in the investigator's judgment, may compromise patient safety or compliance (e.g., severe concurrent illness, abnormal lab results, psychosocial factors).
- •Prior use of PD-1/L1 inhibitors, gemcitabine, nab-paclitaxel, or lenvatinib in adjuvant/neoadjuvant settings.
研究组 & 干预措施
Treatment
Gemcitabine ,nab-Paclitaxel,Lenvatinib and Tislelizumab
干预措施: Gemcitabine nab-PaclitaxelLenvatinibTislelizumab (Drug)
结局指标
主要结局
ORR
时间窗: At the end of Cycle 8 (each cycle is 21 days)
The objective response rate (ORR) of this quadruplet regimen as first-line therapy
次要结局
- Overall Survival (OS)(The end of the 3-year follow-up period)
- Progression-Free Survival (PFS)(At the end of disease progression or death during the 3-year follow-up period)
- Surgical Conversion Rate(At the end of Cycle 8 (each cycle is 21 days))
- Disease control rate (DCR)(At the end of Cycle 8 (each cycle is 21 days))
研究者
Wei Gong
Xinhua Hospital A ffiliated to Shanghai Jiaotong University School of Medicine
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine