Transcatheter Arterial Chemoembolization in Combination With Tislelizumab Plus Lenvatinib Versus Systemic Cisplatin Plus Gemcitabine in Combination With Tislelizumab for Unresectable Intrahepatic Cholangiocarcinoma: A Phase III, Multicenter, Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 140
- 试验地点
- 18
- 主要终点
- Overall Survival
研究概览
简要总结
This is a phase III, multicenter, open-label, randomized controlled trial designed to evaluate the efficacy and safety of arterially directed therapy in combination with tislelizumab plus lenvatinib compared with gemcitabine and cisplatin (GEMCIS) in combination with tislelizumab as first-line treatment for patients with unresectable intrahepatic cholangiocarcinoma.
Approximately 140 eligible patients with histologically confirmed unresectable intrahepatic cholangiocarcinoma without extrahepatic metastasis will be enrolled and randomized in a 1:1 ratio to receive either TACE plus tislelizumab and lenvatinib or GEMCIS plus tislelizumab. In the TACE-based treatment arm, hepatic arterial infusion chemotherapy with gemcitabine and cisplatin may be administered during or after TACE at the investigator's discretion according to the protocol.
The primary endpoint is overall survival. Secondary endpoints include progression-free survival, time to progression, objective response rate, disease control rate, safety, and quality of life.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years.
- •Histologically confirmed intrahepatic cholangiocarcinoma that is unresectable or recurrent after curative treatment, without extrahepatic metastasis.
- •No prior systemic therapy or transarterial interventional therapy for intrahepatic cholangiocarcinoma.
- •At least one measurable intrahepatic lesion according to RECIST v1.
- •ECOG performance status of 0 or
- •Child-Pugh class A liver function.
- •Life expectancy ≥3 months.
- •Adequate hematologic, hepatic, renal, and thyroid function within 14 days before study start, defined as:
- •Absolute neutrophil count ≥1.5 × 10⁹/L;
- •Platelet count ≥75 × 10⁹/L;
- •Hemoglobin ≥90 g/L;
- •Serum albumin ≥30 g/L;
- •Total bilirubin ≤1.5 × upper limit of normal;
- •AST and ALT <1.5 × upper limit of normal, and ALP <4 × upper limit of normal;
- •TSH <1 × upper limit of normal, with T3 and T4 within the normal range;
- •Serum creatinine <1.5 × upper limit of normal and creatinine clearance ≥60 mL/min.
排除标准
- •Diffuse infiltrative liver lesions.
- •Contraindications to TACE.
- •Allergy to intravenous contrast agent.
- •pregnant or breastfeeding women, or participants planning pregnancy within 2 years / unwilling to use effective contraception.
- •Patients with HIV or syphilis infection.
- •Patients with concurrent malignancies or other malignancies within 5 years before enrollment.
- •History of allogeneic organ transplantation.
- •Severe dysfunction of the heart, kidney, or other organs.
- •Severe clinically active infection > grade 2 according to NCI-CTC v5.
- •Psychiatric illness that may affect the informed consent process; Inability to take oral medications; Participation in another drug clinical trial within 12 months before enrollment.
研究组 & 干预措施
Gemcitabine-Cisplatin Plus Tislelizumab
Participants will receive cisplatin 25 mg/m² on Day 1 and Day 8, gemcitabine 1000 mg/m² on Days 1 and 8, and tislelizumab 200 mg on Day 1 of each 3-week cycle for up to 8 cycles. After completion of gemcitabine-cisplatin treatment, participants will continue tislelizumab 200 mg intravenously every 3 weeks. Treatment will continue until clinical progression, radiologic progressive disease according to RECIST v1.1, completion of 2 years of immunotherapy, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria.
干预措施: Cisplatin (Drug)
TACE Plus Tislelizumab and Lenvatinib
Participants will receive tislelizumab 200 mg intravenously every 3 weeks and oral lenvatinib once daily at a starting dose of 12 mg for body weight ≥60 kg or 8 mg for body weight <60 kg. TACE will be performed after initiation of lenvatinib and may be repeated based on radiologic response, residual viable tumor, liver function, and investigator assessment. Both conventional TACE (cTACE) and drug-eluting beads TACE are allowed, and hepatic artery infusion chemotherapy may be added at investigator's discretion. Treatment will continue until clinical progression, radiologic progressive disease according to RECIST v1.1, completion of 2 years of immunotherapy, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria.
干预措施: Transcatheter Arterial Chemoembolization (Procedure)
TACE Plus Tislelizumab and Lenvatinib
Participants will receive tislelizumab 200 mg intravenously every 3 weeks and oral lenvatinib once daily at a starting dose of 12 mg for body weight ≥60 kg or 8 mg for body weight <60 kg. TACE will be performed after initiation of lenvatinib and may be repeated based on radiologic response, residual viable tumor, liver function, and investigator assessment. Both conventional TACE (cTACE) and drug-eluting beads TACE are allowed, and hepatic artery infusion chemotherapy may be added at investigator's discretion. Treatment will continue until clinical progression, radiologic progressive disease according to RECIST v1.1, completion of 2 years of immunotherapy, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria.
干预措施: Hepatic Arterial Infusion Chemotherapy (Procedure)
TACE Plus Tislelizumab and Lenvatinib
Participants will receive tislelizumab 200 mg intravenously every 3 weeks and oral lenvatinib once daily at a starting dose of 12 mg for body weight ≥60 kg or 8 mg for body weight <60 kg. TACE will be performed after initiation of lenvatinib and may be repeated based on radiologic response, residual viable tumor, liver function, and investigator assessment. Both conventional TACE (cTACE) and drug-eluting beads TACE are allowed, and hepatic artery infusion chemotherapy may be added at investigator's discretion. Treatment will continue until clinical progression, radiologic progressive disease according to RECIST v1.1, completion of 2 years of immunotherapy, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria.
干预措施: Tislelizumab (Drug)
TACE Plus Tislelizumab and Lenvatinib
Participants will receive tislelizumab 200 mg intravenously every 3 weeks and oral lenvatinib once daily at a starting dose of 12 mg for body weight ≥60 kg or 8 mg for body weight <60 kg. TACE will be performed after initiation of lenvatinib and may be repeated based on radiologic response, residual viable tumor, liver function, and investigator assessment. Both conventional TACE (cTACE) and drug-eluting beads TACE are allowed, and hepatic artery infusion chemotherapy may be added at investigator's discretion. Treatment will continue until clinical progression, radiologic progressive disease according to RECIST v1.1, completion of 2 years of immunotherapy, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria.
干预措施: Lenvatinib (Drug)
Gemcitabine-Cisplatin Plus Tislelizumab
Participants will receive cisplatin 25 mg/m² on Day 1 and Day 8, gemcitabine 1000 mg/m² on Days 1 and 8, and tislelizumab 200 mg on Day 1 of each 3-week cycle for up to 8 cycles. After completion of gemcitabine-cisplatin treatment, participants will continue tislelizumab 200 mg intravenously every 3 weeks. Treatment will continue until clinical progression, radiologic progressive disease according to RECIST v1.1, completion of 2 years of immunotherapy, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria.
干预措施: Gemcitabine (Drug)
Gemcitabine-Cisplatin Plus Tislelizumab
Participants will receive cisplatin 25 mg/m² on Day 1 and Day 8, gemcitabine 1000 mg/m² on Days 1 and 8, and tislelizumab 200 mg on Day 1 of each 3-week cycle for up to 8 cycles. After completion of gemcitabine-cisplatin treatment, participants will continue tislelizumab 200 mg intravenously every 3 weeks. Treatment will continue until clinical progression, radiologic progressive disease according to RECIST v1.1, completion of 2 years of immunotherapy, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria.
干预措施: Tislelizumab (Drug)
结局指标
主要结局
Overall Survival
时间窗: From randomization to death from any cause, assessed up to approximately 48 months
Overall survival is defined as the time from enrollment/randomization to death from any cause. Participants who withdraw are lost to follow-up or remain alive at the end of the study will be censored at the date they were last known to be alive.
次要结局
- Progression-Free Survival(From randomization to disease progression or death, assessed up to approximately 48 months)
- Time to Progression(From randomization to disease progression, assessed up to approximately 48 months)
- Objective Response Rate(Assessed every 6 weeks ±7 days, up to approximately 48 months)
- Disease Control Rate(Assessed every 6 weeks ±7 days, up to approximately 48 months)
- Incidence of Grade ≥3 Adverse Events(From first dose of study treatment through 28 days after the last dose of study treatment)
- Quality of Life Assessed by EORTC QLQ-C30(Baseline and during treatment/follow-up, assessed up to approximately 48 months)
- Quality of Life Assessed by EQ-5D(Baseline and during treatment/follow-up, assessed up to approximately 48 months)
- Quality of Life Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)(Baseline and during treatment/follow-up, assessed up to approximately 48 months)
- Quality of Life Assessed by the EuroQol Five-Dimension (EQ-5D)(Baseline and during treatment/follow-up, assessed up to approximately 48 months)
研究者
Gao-Jun Teng
Director, Interventional Oncology Center
Zhejiang Cancer Hospital