Efficacy and Safety of HAIC Combined With Lenvatinib and PD-1 Inhibitors for Advanced Intrahepatic Cholangiocarcinoma (LPHAIC for ICC)

Efficacy and Safety of First-line Hepatic Arterial Infusion Chemotherapy With Liposomal Irinotecan Plus 5-FU/LV Combined With Lenvatinib and PD-1 Inhibitors for Advanced Intrahepatic Cholangiocarcinoma

Intrahepatic Cholangiocarcinoma (ICC), the second most prevalent primary malignant liver neoplasm, features highly aggressive biological behavior and dismal prognosis. Even following curative surgical resection, patients have a 5-year overall survival rate lower than 5%, while unresectable patients achieve a median overall survival of only around 6 months. Most patients are diagnosed with locally advanced disease; frequently, surgical resection is contraindicated owing to unfavorable tumor location, vascular invasion or multifocal tumor spread. Therefore, exploring effective therapeutic strategies to boost survival outcomes for such patients is extremely critical.

China carries a heavy disease burden of biliary tract malignancies, with approximately 140,000 newly diagnosed cases each year. The incidence of cholangiocarcinoma exceeds 6 per 100,000 persons (more than 84,000 annual new cases). Moreover, intrahepatic cholangiocarcinoma outnumbers extrahepatic cholangiocarcinoma in incidence, which underscores the urgent demand for optimized treatment strategies.

Hepatic Arterial Infusion Chemotherapy (HAIC) is a regional therapeutic approach. Its theoretical foundation lies in the biological trait that malignant liver tumors are predominantly supplied by the hepatic artery. This modality delivers high-dose chemotherapeutic agents straight to tumor lesions through arterial routes, raising local intratumoral drug concentration and simultaneously reducing systemic adverse toxic reactions.

In recent years, innovations in interventional techniques - especially the application of modified percutaneous hepatic arterial chemotherapy port implantation - have greatly elevated the safety, feasibility and patient adherence of HAIC. Hence, HAIC has attracted extensive attention in treating hepatobiliary malignancies including ICC. Current research focuses on the value of HAIC monotherapy, HAIC combined with systemic chemotherapy, targeted therapy or immunotherapy for unresectable ICC, as well as its potential role as neoadjuvant therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Intrahepatic Cholangiocarcinoma (Icc)
• Intervention / Treatment: Drug: hepatic arterial infusion chemotherapy (Irinotecan liposome plus 5-FU/LV) combined with lenvatinib and PD-1 inhibitors

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

Contacts and Locations

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged between 18 and 80 years old.
• Histologically or cytologically confirmed unresectable locally advanced or intrahepatic cholangiocarcinoma with metastasis.
• Liver function: Child-Pugh Class A (score 5-6) or favorable Class B (score ≤7).
• Have at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

• Estimated survival time > 12 months.

  • No prior systemic therapy for unresectable locally advanced or metastatic intrahepatic cholangiocarcinoma. Patients who received one line of adjuvant or neoadjuvant chemotherapy and experienced recurrence more than 6 months after chemotherapy completion are eligible.
• Adequate bone marrow function: Absolute Neutrophil Count (ANC) ≥ 1.5×10⁹/L, hemoglobin ≥ 90 g/dL, Platelet (PLT) ≥ 100×10⁹/L, White Blood Cell (WBC) ≥ 3.0×10⁹/L.
• Adequate renal function: Serum Creatinine (Cr) ≤ 1.5 × Upper Limit of Normal (ULN), or Creatinine Clearance (CCr) ≥ 60 mL/min (calculated by Cockcroft-Gault formula).
• Adequate coagulation function: Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and International Normalized Ratio (INR) ≤ 1.5 × ULN.
• No active or suspected infection.
• Female patients are not pregnant or breastfeeding. Fertile female and male patients must use effective contraception during the study and for 6 months after the end of study treatment.
• Patients shall have good compliance, be able to understand the study procedures, and provide written informed consent.

Exclusion Criteria:

• Patients with a history of other malignant tumors within the past 5 years, except for cured carcinoma in situ and basal cell carcinoma of the skin.
• Patients with obvious clinical bleeding symptoms or bleeding tendency within 3 months prior to treatment, including bleeding volume > 30 mL, hematemesis, melena, hematochezia, or hemoptysis with fresh blood > 5 mL within 4 weeks.

Patients with a history of venous or arterial thromboembolic events within the preceding 6 months, such as cerebrovascular accidents (transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism.

• Patients requiring long-term anticoagulant therapy with warfarin or heparin, or long-term antiplatelet therapy (aspirin ≥ 300 mg/day or clopidogrel ≥ 75 mg/day).
• Patients with extensive distant metastases (e.g., peritoneal metastasis, multiple bone or brain metastases).
• Patients who have used strong CYP3A4 inducers within 3 weeks before the first dose, or strong CYP3A4 inhibitors / strong UGT1A1 inhibitors within 3 weeks before the first dose.
• Patients who have undergone major organ surgery within 4 weeks prior to treatment (excluding needle biopsy, central venous catheterization, port catheter placement, biliary stenting for biliary obstruction relief, percutaneous transhepatic biliary drainage and cholecystostomy), or those with planned elective surgery.
• Patients with active cardiac diseases within 6 months prior to treatment, including myocardial infarction and severe/unstable angina. Left ventricular ejection fraction < 50% on echocardiography, or uncontrolled arrhythmia.

Patients with congenital or acquired immunodeficiency, such as HIV infection, or active hepatitis (abnormal transaminases; HBV DNA ≥ 1000 IU/mL for hepatitis B, HCV RNA ≥ 1000 IU/mL for hepatitis C).

• Chronic HBV carriers with HBV DNA < 2000 IU/mL are eligible only if they receive concomitant antiviral therapy throughout the study.
• Patients with any other clinically significant metabolic, physical or laboratory abnormalities. At the investigator's discretion, patients with conditions unsuitable for the study drug (e.g., seizures requiring treatment), conditions that may interfere with interpretation of study results, or that place the patient at excessive risk are excluded.
• Patients with intestinal obstruction (excluding incomplete intestinal obstruction managed solely with enteral nutrition), or patients at risk of intestinal perforation (including but not limited to acute diverticulitis, abdominal abscess, and history of abdominal malignancy).
• Pregnant or breastfeeding female subjects.

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: HAIC (Irinotecan liposome plus 5-FU/LV ) combined with lenvatinib and Tislelizumab; HAIC (Hepatic Arterial Infusion Chemotherapy) Irinotecan liposome: 70 mg/m², infused over 90 minutes on Day 1 Leucovorin (LV): 400 mg/m², infused over 2 hours on Day 1 5-Fluorouracil (5-FU): 2400 mg/m², infused over 24 hours on Day 1 Lenvatinib: 8 mg, orally once daily PD-1 inhibitor: 200 mg, infused over 30 minutes on Day 1

Drug: hepatic arterial infusion chemotherapy (Irinotecan liposome plus 5-FU/LV) combined with lenvatinib and PD-1 inhibitors; Each treatment cycle lasts 21 days. Treatment response and tolerability will be evaluated after 2 cycles. The investigator will decide to discontinue treatment or continue for an additional 2-4 cycles accordingly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Proportion of patients with CR or PR assessed by RECIST v1.1 and mRECIST	From enrollment to the end of treatment at 8-12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	Proportion of patients with CR, PR or SD based on RECIST v1.1 and mRECIST	From enrollment to the end of treatment at 8-12 weeks
Adverse events (AEs)	AEs will be graded per NCI-CTCAE v5.0. Evaluate overall AE rate, grade-specific AE rate, Grade ≥3 AE rate and SAE rate.	From enrollment to the end of treatment, up to 6 months
Conversion Resection Rate	Rate of successful radical resection in patients with initially unresectable lesions post treatment	From enrollment to the end of treatment at 12-24 weeks
Progression-Free Survival (PFS)	Time from treatment start to disease progression (RECIST v1.1 and mRECIST)	Time from treatment start to disease progression, up to 6 months
Overall Survival (OS)	Time from treatment initiation to death from any cause.	Time from treatment initiation to death from any cause, an average of 2 years.

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: June 9, 2026
• First Submitted That Met QC Criteria: June 12, 2026
• First Posted (Actual): June 15, 2026

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Lenvatinib; Tislelizumab; Hepatic Arterial Infusion Chemotherapy; HAIC; Intrahepatic Cholangiocarcinoma; Irinotecan Liposome
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma; Cirrhosis, Familial, with Pulmonary Hypertension; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Immune Checkpoint Inhibitors; irinotecan sucrosofate; lenvatinib
• Other Study ID Numbers: E20260006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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