Intraarterial Therapies Plus Tislelizumab Plus Lenvatinib Versus Tislelizumab Plus Gemcitabine-Cisplatin in Unresectable Intrahepatic Cholangiocarcinoma

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Gemcitabine
  Gemcitabine 1000 mg/m² intravenously on Days 1 and 8 of each 21-day cycle, up to 8 cycles.
• Препарат Cisplatin
  Cisplatin 25 mg/m² intravenously on Day 1 and Day 8 of each 21-day cycle, up to 8 cycles.
• Препарат Tislelizumab
  Tislelizumab 200 mg intravenously on Day 1 of each 21-day cycle, followed by maintenance tislelizumab every 3 weeks.
• Препарат Lenvatinib
  Oral lenvatinib once daily, 12 mg for participants with body weight ≥60 kg or 8 mg for participants with body weight \<60 kg, with dose modification according to toxicity.
• Процедура Transcatheter Arterial Chemoembolization
  Conventional TACE or drug-eluting bead TACE are allowed. TACE may be repeated based on imaging assessment every 6 weeks ±7 days and investigator judgment.
• Процедура Hepatic Arterial Infusion Chemotherapy
  Optional hepatic arterial infusion chemotherapy with gemcitabine and cisplatin may be administered during or after TACE at the investigator's discretion according to protocol-defined dose ranges.

Первичные конечные точки

• Overall Survival [Срок оценки: From randomization to death from any cause, assessed up to approximately 48 months]

Вторичные конечные точки (7)

• Progression-Free Survival [Срок оценки: From randomization to disease progression or death, assessed up to approximately 48 months]
• Time to Progression [Срок оценки: From randomization to disease progression, assessed up to approximately 48 months]
• Objective Response Rate [Срок оценки: Assessed every 6 weeks ±7 days, up to approximately 48 months]
• Disease Control Rate [Срок оценки: Assessed every 6 weeks ±7 days, up to approximately 48 months]
• Incidence of Grade ≥3 Adverse Events [Срок оценки: From first dose of study treatment through 28 days after the last dose of study treatment]
• Quality of Life Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [Срок оценки: Baseline and during treatment/follow-up, assessed up to approximately 48 months]
• Quality of Life Assessed by the EuroQol Five-Dimension (EQ-5D) [Срок оценки: Baseline and during treatment/follow-up, assessed up to approximately 48 months]

Критерии участия

Критерии включения

• 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 v1.1.
• ECOG performance status of 0 or 1.
• 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.

Критерии исключения

• 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 v5.0.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 18 центров

• The First Affiliated Hospital, Sun Yat-sen University — Гуанчжоу
• Jinshazhou Hospital of Guangzhou University of Chinese Medicine — Гуанчжоу
• Guangdong Second People's Hospital — Гуанчжоу
• The Affiliated Panyu Central Hospital of Guangzhou Medical University — Гуанчжоу
• The Second Affiliated Hospital of Guangdong Medical University — Гуанчжоу
• Jiangmen Central Hospital — Jiangmen
• Wuhan Union Hospital of China — Ухань
• The Second Xiangya Hospital of Central South University — Чанша
• … и ещё 10 центров

Идентификаторы

NCT: NCT07691515 · RAINBOW 01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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