Hepatic Arterial Infusion Chemotherapy (HAIC) Sequential Small-Sized Drug-Eluting Beads Transarterial Chemoembolization (DEB-TACE) Combined With Toripalimab and Lenvatinib for Unresectable Intrahepatic Cholangiocarcinoma: A Phase II Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 29
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
Purpose: This phase II clinical trial evaluates whether a combination of liver-directed local therapies (HAIC and DEB-TACE) with immunotherapy (toripalimab) and targeted therapy (lenvatinib) is safe and effective for patients with unresectable intrahepatic cholangiocarcinoma (a type of liver cancer that cannot be removed by surgery).
Participants: Adults aged 18-85 years with pathologically confirmed unresectable intrahepatic cholangiocarcinoma, no prior immune checkpoint inhibitor therapy, and adequate organ function.
Study details include:
Study Duration: Up to 24 months per participant
Treatment Duration: Up to 6 cycles (each cycle is 21 days) of combination therapy, followed by maintenance therapy with toripalimab and lenvatinib until disease progression or unacceptable toxicity
Visit Frequency: Every 3 weeks during the treatment phase; tumor imaging assessments every 6-8 weeks
Primary endpoints: Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Safety will be assessed by monitoring adverse events graded according to NCI-CTCAE v5.0.
Toripalimab and lenvatinib are not available through an expanded access program.
详细描述
Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy. Most patients are diagnosed at locally advanced or metastatic stages, precluding curative surgical resection. For unresectable ICC, conventional chemotherapy offers limited efficacy, with a 5-year survival rate below 10%. Emerging evidence suggests that combining locoregional therapies with immunotherapy and targeted therapy may improve outcomes.
Study Design: This is a prospective, single-arm, single-center, phase II exploratory clinical trial. Approximately 29 evaluable patients will be enrolled at Zhongshan Hospital, Fudan University.
Intervention: Participants will receive a comprehensive treatment regimen consisting of:
HAIC (Hepatic Arterial Infusion Chemotherapy): Oxaliplatin 85 mg/m² and gemcitabine (total 1000 mg/m², with a portion used for DEB-TACE loading) administered via hepatic artery infusion over ≥2 hours on Day 1 of each 21-day cycle, for up to 6 cycles.
DEB-TACE (Drug-Eluting Beads Transarterial Chemoembolization): Small-sized (40-90 μm) drug-eluting beads loaded with gemcitabine, performed on Day 1 of each cycle as needed (required in Cycle 1, thereafter based on tumor vascularity and imaging assessment).
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary participation and signed informed consent.
- •Age 18 to 85 years.
- •Pathologically confirmed intrahepatic cholangiocarcinoma.
- •Imaging-confirmed unresectable locally advanced intrahepatic cholangiocarcinoma with measurable lesions (longest diameter ≥10 mm) per RECIST 1.
- •No distant organ metastases (excluding lymph node metastases).
- •Child-Pugh liver function grade A or good B (≤7 points).
- •ECOG performance status score 0-1 within 1 week before enrollment.
- •Expected survival ≥12 weeks.
- •No prior treatment with immune checkpoint inhibitors (including PD-1/PD-L1 antibodies and CTLA-4 inhibitors).
- •Laboratory values within 7 days before enrollment meeting the following criteria:
- •ANC ≥1.0×10⁹/L; platelets ≥50×10⁹/L; hemoglobin ≥90 g/L (without transfusion or G-CSF within 14 days before screening).
- •Serum albumin ≥30 g/L; total bilirubin ≤1.5×ULN; ALT and AST ≤5×ULN; serum creatinine ≤1.5×ULN or CrCl >50 mL/min (Cockcroft-Gault formula).
- •INR ≤2.3 or PT prolonged ≤6 seconds above normal range.
- •Urine protein <2+ (if ≥2+, 24-hour quantification <1.0 g allowed).
排除标准
- •Received other local treatments (excluding surgery) within 1 month before study entry. Prior TAE/TAI not allowed. Prior TACE >3 times not allowed.
- •Prior systemic anti-tumor therapy (including targeted therapy, immunotherapy, chemotherapy).
- •Concurrent or prior other malignancy within 5 years.
- •Active autoimmune disease or history of autoimmune disease with potential relapse.
- •Clinically symptomatic moderate-to-severe ascites requiring therapeutic paracentesis/drainage or Child-Pugh score >2; uncontrolled or moderate-to-large pleural/pericardial effusion.
- •History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months before study treatment.
- •History of thrombosis or embolic events (e.g., cerebrovascular accident including TIA, cerebral hemorrhage, cerebral infarction, pulmonary embolism) within 6 months before study treatment.
- •Known inherited or acquired bleeding disorder or thrombotic tendency; currently or recently (within 10 days) receiving full-dose anticoagulants or thrombolytics for therapeutic purposes (prophylactic low-dose aspirin or LMWH allowed).
- •Major vascular disease within 6 months before study treatment (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis).
- •Severe, non-healing, or dehisced wounds, active ulcers, or untreated fractures.
- •Major surgery within 4 weeks before study treatment (excluding diagnostic) or anticipated need for major surgery during the study.
- •History of intestinal obstruction or clinical signs/symptoms of GI obstruction within 6 months before study treatment.
- •History of hepatic encephalopathy.
- •Palliative radiotherapy for non-target lesions allowed only if completed ≥2 weeks before study treatment and AEs recovered to ≤CTCAE grade
- •Severe infection within 4 weeks before study treatment, including hospitalization for infection, bacteremia, or severe pneumonia; oral or IV therapeutic antibiotics within 2 weeks (prophylactic allowed).
- •Congenital or acquired immunodeficiency (e.g., HIV infection).
- •Palliative radiotherapy involving >5% of bone marrow area within 4 weeks for patients with bone metastases.
- •Received live attenuated vaccine within 28 days before study treatment, or expected to receive such vaccine during toripalimab treatment or within 60 days after last dose.
- •Received other investigational drugs within 28 days before study treatment.
- •Other factors judged by the investigator that may affect study results or cause premature termination, such as alcoholism, drug abuse, other serious diseases (including psychiatric) requiring concomitant treatment, severe laboratory abnormalities, family or social factors affecting patient safety.
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: From the start of treatment until disease progression, up to 24 months
Proportion of participants achieving a confirmed complete response (CR) or partial response (PR) according to RECIST 1.1 and mRECIST criteria, assessed by the investigator. This is the primary efficacy endpoint used for sample size calculation.
Progression-Free Survival (PFS)
时间窗: From enrollment until disease progression or death, assessed up to 24 months
Time from enrollment to first documented disease progression per RECIST 1.1 and mRECIST criteria, or death from any cause, whichever occurs first.
Overall Survival (OS)
时间窗: From enrollment until death, assessed up to 24 months
Time from enrollment to death from any cause.
次要结局
- Disease Control Rate (DCR)(From the start of treatment until disease progression, up to 24 months)
- Duration of Response (DoR)(From first response until disease progression or death, assessed up to 24 months)
- Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)(From the time of informed consent until 30 days after the last dose of study treatment, or until resolution/return to baseline, assessed up to 24 months)