A Study of Liposomal Irinotecan Plus 5-FU/LV HAIC With Lenvatinib and a PD-1 Inhibitor in Advanced ICC

A Prospective Study on the Efficacy and Safety of Liposomal Irinotecan, 5-Fluorouracil, and Leucovorin Hepatic Arterial Infusion Chemotherapy (HAIC) Combined With Lenvatinib and a PD-1 Inhibitor as First-Line Therapy for Advanced Intrahepatic Cholangiocarcinoma (ICC)

This is a prospective, single-center, single-arm clinical study. It aims to evaluate the efficacy and safety of a new combination therapy as a first-line treatment for patients with advanced intrahepatic cholangiocarcinoma (ICC) who cannot be treated with surgery. The combined therapy includes hepatic arterial infusion chemotherapy (HAIC) with Liposomal Irinotecan, 5-Fluorouracil, and Leucovorin, along with the oral targeted drug Lenvatinib and an intravenous PD-1 inhibitor (an immunotherapy). A total of 30 participants will be enrolled. The main goal of the study is to measure the Objective Response Rate (ORR), which is the percentage of patients whose cancer shrinks or disappears after treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Other: Hepatic Arterial Infusion Chemotherapy (HAIC) with Liposomal Irinotecan, 5-Fluorouracil, Leucovorin; Drug: Lenvatinib; Drug: PD-1 Inhibitor

Detailed Description

This study investigates a novel therapeutic strategy for unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma (ICC). Despite being the second most common primary liver malignancy, advanced ICC has a poor prognosis with limited effective first-line treatment options. The rationale for this combination regimen is based on the potential synergy between localized and systemic therapies. Hepatic arterial infusion chemotherapy delivers high concentrations of chemotherapy directly to the liver tumors, potentially improving local control while reducing systemic toxicity. The combination of Lenvatinib, a multi-targeted tyrosine kinase inhibitor, and a PD-1 inhibitor is designed to simultaneously inhibit tumor angiogenesis and enhance anti-tumor immunity. This study will explore whether combining these modalities (HAIC + targeted therapy + immunotherapy) can yield superior efficacy compared to historical data of standard chemotherapy. The liposomal formulation of irinotecan is utilized for its improved pharmacokinetic profile and targeted delivery, which may enhance efficacy and tolerability. Key assessments include tumor evaluation based on RECIST 1.1 criteria and safety monitoring per NCI CTCAE v5.0.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18 to 75 years.
2. Histologically or cytologically confirmed unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma (ICC).
3. Liver function: Child-Pugh class A (score 5-6) or good class B (score ≤7).
4. At least one measurable lesion as defined by RECIST 1.1 criteria.
5. ECOG performance status of 0 or 1.
6. Life expectancy greater than 12 months.
7. No prior systemic therapy for unresectable locally advanced or metastatic ICC. Prior adjuvant or neoadjuvant chemotherapy is allowed if completed >6 months before recurrence.
8. Adequate bone marrow function: Absolute Neutrophil Count (ANC) ≥1.5×10⁹/L, Hemoglobin ≥90 g/L, Platelet count (PLT) ≥100×10⁹/L, White Blood Cell count (WBC) ≥3.0×10⁹/L.
9. Adequate renal function: Serum creatinine (Cr) ≤1.5 × ULN or Creatinine Clearance (CCr) ≥60 mL/min (calculated by Cockcroft-Gault formula).
10. Adequate coagulation function: Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), and International Normalized Ratio (INR) ≤1.5 × ULN.
11. No active or suspected infection.
12. Not pregnant or lactating. Female and male participants of childbearing potential must use effective contraception during the study and for 6 months after the last dose.
13. Good compliance, ability to understand the study procedures, and provision of signed informed consent.

Exclusion Criteria:

1. History of other malignancies within the past 5 years (except cured carcinoma in situ or basal cell skin cancer).
2. Significant clinical bleeding symptoms or tendency within 3 months prior to treatment (e.g., >30 mL bleeding, hematemesis, melena, hematochezia), hemoptysis (>5 mL of fresh blood within 4 weeks). Venous/thrombotic events within the past 6 months (e.g., cerebrovascular accident, deep vein thrombosis, pulmonary embolism). Requirement for long-term anticoagulation (e.g., warfarin, heparin) or antiplatelet therapy (Aspirin ≥300 mg/day or Clopidogrel ≥75 mg/day).
3. Extensive distant metastasis (e.g., peritoneal metastasis, multiple bone/brain metastases).
4. Use of strong CYP3A4 inducers within 3 weeks prior to first dose, or use of strong CYP3A4 inhibitors or strong UGT1A1 inhibitors within 3 weeks prior to first dose.
5. Major organ surgery within 4 weeks prior to treatment (excluding needle biopsy, central venous catheter placement, port implantation, biliary stenting, percutaneous transhepatic biliary drainage, cholecystostomy) or planned elective surgery.
6. Active cardiac disease within 6 months prior to treatment, including myocardial infarction, severe/unstable angina. Left ventricular ejection fraction (LVEF) <50% by echocardiogram, or poorly controlled arrhythmia.
7. Congenital or acquired immunodeficiency (e.g., HIV infection), or active hepatitis (abnormal liver enzymes; for Hepatitis B: HBV DNA ≥1000 IU/mL; for Hepatitis C: HCV RNA ≥1000 IU/mL). Chronic HBV carriers with HBV DNA <2000 IU/ml can be enrolled if they receive concurrent antiviral therapy during the trial.
8. Any other disease, metabolic disorder, physical examination finding, or laboratory abnormality that, in the investigator's judgment, contraindicates the use of the study drug, may affect result interpretation, or places the patient at high risk.
9. Bowel obstruction (except incomplete obstruction manageable with enteral nutrition) or patients at risk of bowel perforation (e.g., acute diverticulitis, abdominal abscess, history of abdominal cancer).
10. Pregnant or lactating female participants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combination Therapy Group; All participants receive the combined regimen of hepatic arterial infusion chemotherapy (HAIC) with Liposomal Irinotecan, 5-Fluorouracil, and Leucovorin, plus oral Lenvatinib and an intravenous PD-1 inhibitor as first-line treatment.

Other: Hepatic Arterial Infusion Chemotherapy (HAIC) with Liposomal Irinotecan, 5-Fluorouracil, Leucovorin; Liposomal Irinotecan (70 mg/m²) infused over 90 minutes, followed by Leucovorin (400 mg/m²) infused over 2 hours, and then 5-Fluorouracil (2400 mg/m²) infused over 24 hours via hepatic arterial infusion on Day 1 of each 21-day cycle. The number of treatment cycles (2 to 6) is determined by the investigator based on tumor response and tolerability after the initial 2 cycles.; Drug: Lenvatinib; Lenvatinib is administered orally at a dose of 8 mg once daily, continuously throughout each 21-day cycle.; Drug: PD-1 Inhibitor; A PD-1 inhibitor (specific agent chosen at the investigator's discretion) is administered via intravenous infusion on Day 1 of each 21-day cycle, approximately 24 hours prior to the initiation of HAIC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR)	Every 2 cycles (each cycle is 21 days ) during the treatment period

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-Free Survival (PFS)	From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Overall Survival (OS)	From date of first dose until the date of death from any cause, assessed up to 60 months
Disease Control Rate (DCR)	From date of first dose until the date of first documented progression or the end of treatment, whichever came first, assessed up to 24 months
Conversion Resection Rate	From date of first dose until the date of radical surgery, assessed up to 24 months

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 9, 2026
• Primary Completion (Estimated): June 9, 2032
• Study Completion (Estimated): August 9, 2032

Study Registration Dates

• First Submitted: February 2, 2026
• First Submitted That Met QC Criteria: February 23, 2026
• First Posted (Actual): February 25, 2026

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Hepatic Arterial Infusion Chemotherapy(HAIC), Liposomal Irinotecan, 5-Fluorouracil, Leucovorin, Lenvatinib, PD-1 Inhibitor, Immunotherapy, Targeted Therapy
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Enzymes and Coenzymes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Immune Checkpoint Inhibitors; Fluorouracil; Leucovorin; lenvatinib
• Other Study ID Numbers: CSPC-DNY-BTC-TJ03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Yes. De-identified individual participant data that underlie the results reported in the primary publication (including data dictionaries) will be made available upon reasonable request to qualified researchers. Proposals should be directed to 210412103@sust.edu.cn. Data will be available beginning 12 months after article publication, with no end date. Requestors will need to sign a data access agreement and obtain approval from an institutional review board.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No