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

Official title

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

Overview

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.

Interventions

• Drug Gemcitabine
  Gemcitabine 1000 mg/m² intravenously on Days 1 and 8 of each 21-day cycle, up to 8 cycles.
• Drug Cisplatin
  Cisplatin 25 mg/m² intravenously on Day 1 and Day 8 of each 21-day cycle, up to 8 cycles.
• Drug Tislelizumab
  Tislelizumab 200 mg intravenously on Day 1 of each 21-day cycle, followed by maintenance tislelizumab every 3 weeks.
• Drug 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.
• Procedure 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.
• Procedure 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.

Primary outcome measures

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

Secondary outcome measures (7)

• Progression-Free Survival [Time frame: From randomization to disease progression or death, assessed up to approximately 48 months]
• Time to Progression [Time frame: From randomization to disease progression, assessed up to approximately 48 months]
• Objective Response Rate [Time frame: Assessed every 6 weeks ±7 days, up to approximately 48 months]
• Disease Control Rate [Time frame: Assessed every 6 weeks ±7 days, up to approximately 48 months]
• Incidence of Grade ≥3 Adverse Events [Time frame: 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) [Time frame: Baseline and during treatment/follow-up, assessed up to approximately 48 months]
• Quality of Life Assessed by the EuroQol Five-Dimension (EQ-5D) [Time frame: Baseline and during treatment/follow-up, assessed up to approximately 48 months]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 18 centers

• The First Affiliated Hospital, Sun Yat-sen University — Guangzhou
• Jinshazhou Hospital of Guangzhou University of Chinese Medicine — Guangzhou
• Guangdong Second People's Hospital — Guangzhou
• The Affiliated Panyu Central Hospital of Guangzhou Medical University — Guangzhou
• The Second Affiliated Hospital of Guangdong Medical University — Guangzhou
• Jiangmen Central Hospital — Jiangmen
• Wuhan Union Hospital of China — Wuhan
• The Second Xiangya Hospital of Central South University — Changsha
• … and 10 more centers

Identifiers

NCT: NCT07691515 · RAINBOW 01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗