HAIC Plus Systemic Chemotherapy, Lenvatinib and Toripalimab in Advanced ICC

Systemic Chemotherapy, Lenvatinib and Toripalimab With or Without Hepatic Arterial Infusion In Advanced Intrahepatic Cholangiocarcinoma: A Prospective, Randomized, Two-Cohort, Phase II Study.

Prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) remains poor. Treatment combination known as Gemox (systemic chemotherapy of gemcitabine and oxaliplatin), along with lenvatinib and toripalimab, has shown favor results for ICC patients. However, Hepatic Arterial Infusion Chemotherapy (HAIC), which delivers chemotherapy directly to the liver, has also demonstrated benefits in controlling the cancer locally and improving survival for patients with ICC.

Based on these promising approaches, this study aims to find out if adding HAIC to the systemic chemotherapy-based treatment can help extending patients survival.

Study Overview

• Status: Completed
• Conditions: Intrahepatic Cholangiocarcinoma (Icc)
• Intervention / Treatment: Procedure: hepatic arterial infusion chemotherapy (HAIC); Drug: Chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Cancer Center Sun Yat-sen University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically proven ICC with locally advanced or metastatic disease deemed unresectable by multidisciplinary evaluation; At least one measurable disease according to the Response Evaluation Criteria in Solid Tumors（RECIST v1.1）; Child-Pugh class A or B; ECOG performance status 0-1; Adequate bone marrow function（white blood cell count ≥2,000cells/mm3, hemoglobin > 9.0 g/dL, Platelet count ≥75,000/mm3）; Adequate hepatic and renal function (albumin ≥ 30 g/L, total bilirubin < 3 times the upper limit of normal, aspartate and alanine transaminases < 5 times the upper limit of normal, creatinine clearance rate of ≤ 1.5 times the upper limit of the normal) and coagulation function（PT < 18s, INR < 1.26）; written informed consent.

Exclusion Criteria:

• Life expectancy less than 2 months; concurrent other malignancy; Prior anticancer therapy (including chemotherapy, radiotherapy, surgery, or interventional treatments); Known allergy to chemotherapy drugs, lenvatinib or PD-(L)1 inhibitors; Patients with uncontrolled comorbidities, active infections; pregnancy or lactation; Refuse to comply with study and/or follow-up procedures; Gastrointestinal bleeding of any grade within 4 weeks prior to the treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental arm: Hepatic arterial infusion plus systemic chemotherapy, lenvatinib and toripalimab	Procedure: hepatic arterial infusion chemotherapy (HAIC); Hepatic arterial infusion chemotherapy: oxaliplatin 85mg/m2 via HAIC pump for 3 hours on day 1; Q3W Drug: Gemcitabine 1g/m2 intravenously on day 1 and day 8 of a 3 weeks cycle Drug: Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing Drug: Toripalimab 240 mg iv.drip Q3W
Active Comparator: Control arm: Gemox plus lenvatinib and toripalimab	Drug: Chemotherapy; Systemic chemotherapy of GemOx regimen: oxaliplatin 85mg/m2 and gemcitabine 1g/m2 intravenously on day 1, and gemcitabine 1g/m2 intravenously on day 8 of a 3 weeks cycle. Drug: Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing Drug: Toripalimab 240 mg iv.drip Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-months PFS	6-months Progression-Free Survival Rate (6-months PFS rate) is defined as the proportion of patients who remain alive and free from disease progression (as assessed by RECIST v1.1) at 6 months from the initiation of study randomization.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Number of adverse events. Postoperative adverse events were graded based on CTCAE v5.0	30 days
Overall Survival (OS)	OS was defined as the duration from the date of randomization until the date of death from any cause. Participants who were lost to follow-up were censored at the last date the participant was known to be alive, and participants who remained alive were censored at the time of data cutoff.	18 months
Progression Free Survival (PFS)	PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), or date of death, whichever occurred first.	18 months
Objective Response Rate (ORR)	ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on RECIST. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference to the baseline sum of the diameters of target lesions.	18 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2023
• Primary Completion (Actual): April 1, 2025
• Study Completion (Actual): June 1, 2025

Study Registration Dates

• First Submitted: December 11, 2025
• First Submitted That Met QC Criteria: December 24, 2025
• First Posted (Estimated): December 26, 2025

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 29, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: immunotherapy; lenvatinib; HAIC; combined therapy; GemOx
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma; Cirrhosis, Familial, with Pulmonary Hypertension; Therapeutics; Drug Therapy
• Other Study ID Numbers: IA3GM-II

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No