HAIC + DEB-TACE + Toripalimab + Lenvatinib for Unresectable Intrahepatic Cholangiocarcinoma

Summary

Purpose: This phase II clinical trial evaluates whether a combination of liver-directed local therapies (HAIC and DEB-TACE) with immunotherapy (toripalimab) and targeted therapy (lenvatinib) is safe and effective for patients with unresectable intrahepatic cholangiocarcinoma (a type of liver cancer that cannot be removed by surgery).

Participants: Adults aged 18-85 years with pathologically confirmed unresectable intrahepatic cholangiocarcinoma, no prior immune checkpoint inhibitor therapy, and adequate organ function.

Study details include:

Study Duration: Up to 24 months per participant

Treatment Duration: Up to 6 cycles (each cycle is 21 days) of combination therapy, followed by maintenance therapy with toripalimab and lenvatinib until disease progression or unacceptable toxicity

Visit Frequency: Every 3 weeks during the treatment phase; tumor imaging assessments every 6-8 weeks

Primary endpoints: Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Safety will be assessed by monitoring adverse events graded according to NCI-CTCAE v5.0.

Toripalimab and lenvatinib are not available through an expanded access program.

Conditions

• Liver Cancer

Interventions

DEVICE

DEB-TACE

Small-sized (40-90 μm) drug-eluting beads loaded with gemcitabine, administered via transarterial chemoembolization into the hepatic artery to occlude tumor blood vessels and deliver localized chemotherapy. Performed on Day 1 of each 21-day cycle as needed (required in Cycle 1, thereafter based on tumor vascularity and imaging assessment).

DRUG

Toripalimab

200 mg administered as an intravenous infusion on Day 1 of each 21-day cycle. Toripalimab is a humanized anti-PD-1 monoclonal antibody that blocks PD-1/PD-L1 interaction, restoring T-cell anti-tumor immune activity.

DRUG

Lenvatinib

Oral daily dosing: 8 mg/day for body weight \<60 kg; 12 mg/day for body weight ≥60 kg. Lenvatinib is a multi-target tyrosine kinase inhibitor that inhibits VEGFR1-3, FGFR1-4, PDGFRα, KIT, and RET, thereby reducing tumor angiogenesis and suppressing tumor cell proliferation.

DRUG

Gemcitabine

Total dose 1000 mg/m² administered via hepatic artery infusion (HAIC) on Day 1 of each 21-day cycle, for up to 6 cycles. A portion of the dose is used for DEB-TACE drug loading; the remainder is administered via HAIC. Gemcitabine is a pyrimidine nucleoside analog that inhibits DNA synthesis and induces tumor cell apoptosis.

DRUG

Oxaliplatin

85 mg/m² administered via hepatic artery infusion (HAIC) on Day 1 of each 21-day cycle, for up to 6 cycles. Oxaliplatin is a third-generation platinum-based chemotherapeutic agent that forms DNA crosslinks, blocking DNA replication and transcription, and inducing tumor cell apoptosis.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-06-30

Primary Completion

2028-06-30

Completion

2028-12-31