Intrahepatic Cholangiocarcinoma (Icc)
Conditions
Keywords
Intrahepatic Cholangiocarcinoma, randomized controlled trial, Transcatheter Arterial Chemoembolization, Tislelizumab, Lenvatinib, GemCis
Brief summary
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
DRUGGemcitabine
Gemcitabine 1000 mg/m² intravenously on Days 1 and 8 of each 21-day cycle, up to 8 cycles.
DRUGCisplatin
Cisplatin 25 mg/m² intravenously on Day 1 and Day 8 of each 21-day cycle, up to 8 cycles.
DRUGTislelizumab
Tislelizumab 200 mg intravenously on Day 1 of each 21-day cycle, followed by maintenance tislelizumab every 3 weeks.
DRUGLenvatinib
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.
PROCEDURETranscatheter 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.
PROCEDUREHepatic 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.
Sponsors
Zhejiang Cancer Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years. 2. Histologically confirmed intrahepatic cholangiocarcinoma that is unresectable or recurrent after curative treatment, without extrahepatic metastasis. 3. No prior systemic therapy or transarterial interventional therapy for intrahepatic cholangiocarcinoma. 4. At least one measurable intrahepatic lesion according to RECIST v1.1. 5. ECOG performance status of 0 or 1. 6. Child-Pugh class A liver function. 7. Life expectancy ≥3 months. 8. 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
1. Diffuse infiltrative liver lesions. 2. Contraindications to TACE. 3. Allergy to intravenous contrast agent. 4. pregnant or breastfeeding women, or participants planning pregnancy within 2 years / unwilling to use effective contraception. 5. Patients with HIV or syphilis infection. 6. Patients with concurrent malignancies or other malignancies within 5 years before enrollment. 7. History of allogeneic organ transplantation. 8. Severe dysfunction of the heart, kidney, or other organs. 9. Severe clinically active infection \> grade 2 according to NCI-CTC v5.0. 10. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | From randomization to disease progression or death, assessed up to approximately 48 months | 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 to Progression | From randomization to disease progression, assessed up to approximately 48 months | 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. |
| Objective Response Rate | Assessed every 6 weeks ±7 days, up to approximately 48 months | Defined as the proportion of participants achieving complete response or partial response according to RECIST v1.1. |
| Disease Control Rate | Assessed every 6 weeks ±7 days, up to approximately 48 months | Defined as the proportion of participants achieving complete response, partial response, or stable disease according to RECIST v1.1. |
| Incidence of Grade ≥3 Adverse Events | From first dose of study treatment through 28 days after the last dose of study treatment | Defined as the occurrence of grade 3 or higher hematologic or non-hematologic toxicities, graded according to CTCAE v5.0. |
| 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 | 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. |
| Quality of Life Assessed by the EuroQol Five-Dimension (EQ-5D) | Baseline and during treatment/follow-up, assessed up to approximately 48 months | 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. |
Countries
China
Contacts
CONTACTGaojun Teng, MD
CONTACTBinyan Zhong, MD
PRINCIPAL_INVESTIGATORGaojun Teng, MD
Zhejiang Cancer Hospital
PRINCIPAL_INVESTIGATORMin Kuang, MD
First Affiliated Hospital, Sun Yat-Sen University
PRINCIPAL_INVESTIGATORJiansong Ji, MD
The Central Hospital of Lishui City
Outcome results
None listed