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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
140
Gemcitabine 1000 mg/m² intravenously on Days 1 and 8 of each 21-day cycle, up to 8 cycles.
Cisplatin 25 mg/m² intravenously on Day 1 and Day 8 of each 21-day cycle, up to 8 cycles.
Tislelizumab 200 mg intravenously on Day 1 of each 21-day cycle, followed by maintenance tislelizumab every 3 weeks.
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.
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.
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.
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China
Jinshazhou Hospital of Guangzhou University of Chinese Medicine
Guangzhou, Guangdong, China
Guangdong Second People's Hospital
Guangzhou, Guangdong, China
The Affiliated Panyu Central Hospital of Guangzhou Medical University
Guangzhou, Guangdong, China
The Second Affiliated Hospital of Guangdong Medical University
Guangzhou, Guangdong, China
Jiangmen Central Hospital
Jiangmen, Guangdong, China
Wuhan Union Hospital of China
Wuhan, Hubei, China
The Second Xiangya Hospital of Central South University
Changsha, Hunan, China
The Third Xiangya Hospital of Central South University
Changsha, Hunan, China
Ganzhou Hospital-Nanfang Hospital, Southern Medical University
Ganzhou, Jiangxi, China
...and 8 more locations
Overall Survival
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.
Time frame: From randomization to death from any cause, assessed up to approximately 48 months
Progression-Free Survival
Defined as the time from randomization to disease progression or death from any cause. Participants without progression or death will be censored at the last date known to be progression-free.
Time frame: From randomization to disease progression or death, assessed up to approximately 48 months
Time to Progression
Defined as the time from randomization to disease progression. Participants who die without prior progression, withdraw, are lost to follow-up, or remain progression-free at study end will be censored at the last date known to be progression-free.
Time frame: From randomization to disease progression, assessed up to approximately 48 months
Objective Response Rate
Defined as the proportion of participants achieving complete response or partial response according to RECIST v1.1.
Time frame: Assessed every 6 weeks ±7 days, up to approximately 48 months
Disease Control Rate
Defined as the proportion of participants achieving complete response, partial response, or stable disease according to RECIST v1.1.
Time frame: Assessed every 6 weeks ±7 days, up to approximately 48 months
Incidence of Grade ≥3 Adverse Events
Defined as the occurrence of grade 3 or higher hematologic or non-hematologic toxicities, graded according to CTCAE v5.0.
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)
The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 is a 30-item questionnaire used to assess health-related quality of life in patients with cancer. Scores are linearly transformed to a 0 to 100 scale. For the global health status/quality-of-life scale and functional scales, higher scores indicate better health-related quality of life or functioning. For symptom scales and single symptom items, higher scores indicate a higher symptom burden or worse symptoms.
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)
The EuroQol Five-Dimension Three-Level Questionnaire is a standardized instrument for measuring health-related quality of life. The descriptive system includes five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored from 1 to 3, where 1 indicates no problems, 2 indicates some or moderate problems, and 3 indicates extreme problems or inability to perform the activity. Higher scores in each dimension indicate more severe problems or worse health status.
Time frame: Baseline and during treatment/follow-up, assessed up to approximately 48 months
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