Hepatic Arterial Infusion Chemotherapy (HAIC) Combined With Durvalumab and Lenvatinib in Patients With Locally Advanced or Metastatic Intrahepatic Cholangiocarcinoma: a Phase 2 Study(HAIC-quad Trial) (HAIC-quad)

At present, the first-line treatment for patients with advanced unresectable intrahepatic cholangiocarcinoma is mainly systemic treatment, but the improvement in efficacy is limited and is not enough to meet the current clinical treatment needs. Hepatic artery infusion chemotherapy (HAIC) has the advantages of increasing local drug concentration and reducing toxic side effects compared to systemic intravenous chemotherapy. In order to enable patients with advanced intrahepatic cholangiocarcinoma to obtain better treatment effects, this study plans to explore HAIC combined with durvalumab and lenvatinib as the first-line treatment for patients with locally advanced or metastatic ICC, in order to provide a better treatment choice for their comprehensive treatment.

Study Overview

• Status: Recruiting
• Conditions: Durvalumab; Intrahepatic Cholangiocarcinoma (Icc); HAIC
• Intervention / Treatment: Drug: Durvalumab; Drug: hepatic arterial infusion chemotherapy (HAIC); Drug: Lenvatinib

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yun X Zhang, PHD; Phone Number: 18011410585; Email: zhangxiaoyun@wchscu.cn

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China
      • Recruiting
      • West China Hospital, Sichuan University
      • Contact: yun X Zhang, PHD; Phone Number: +86-18011410585; Email: zhangxiaoyun@wchscu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histologically confirmed intrahepatic cholangiocarcinoma, with a preliminary diagnosis of unresectable or metastatic disease and no previous systemic treatment.

   Anatomical factors: ① Patients with invasion of the portal vein, hepatic vein or main bile duct, who cannot undergo resection and reconstruction; ② Patients with decompensated cirrhosis or severe portal hypertension, and the residual liver FLR does not meet the safe liver resection decision-making system Biological factors: ① Multiple tumors in the left and right livers; ② Metastasis to distant lymph nodes such as the para-aorta or distant organ metastasis

2. Disease recurrence > 6 months after radical surgery; if adjuvant therapy is given after surgery, patients > 6 months after completion of adjuvant therapy (chemotherapy and/or radiotherapy) are eligible for inclusion.
3. WHO/ECOG PS of 0 or 1
4. There was at least 1 target lesion (TL) that met the RECIST 1.1 criteria

Exclusion Criteria:

1. Patients who have received systemic treatment in the past.
2. Patients with severe liver dysfunction (Child-Pugh C grade), or significant jaundice, hepatic encephalopathy, refractory ascites, or hepatorenal syndrome.
3. Patients with severe and uncorrectable coagulation dysfunction.
4. Patients with active hepatitis or severe infection who cannot be treated simultaneously.
5. Patients with cachexia or multiple organ failure.

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-quad Arm

Drug: Durvalumab; Durvalumab: During combination therapy: 1500 mg, Q3W, during combination therapy, on days 3-5 of each 3-week cycle (determined by the investigator); during maintenance therapy: 1500 mg Q4W; Drug: hepatic arterial infusion chemotherapy (HAIC); hepatic arterial infusion chemotherapy (HAIC) : GemCis regimen was adopted, with the specific regimen as follows: cisplatin 60 mg/m2 on the first day, arterial infusion for half an hour, gemcitabine 1000 mg/m2 on the first day, arterial infusion for half an hour, repeated once every 3 weeks, and 4-6 cycles of treatment (the specific number of cycles was determined by the investigator according to the patient's condition).; Drug: Lenvatinib; Lenvatinib 8mg (weight <60 kg) or 12mg (weight ≥60 kg) oral QD, during combination therapy, starting on day 3 of each 3-week cycle (determined by the investigator)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Disease assessments based on investigator assessments were determined by using RECIST version 1.1 guidelines. The ORR was defined as the percentage of patients with confirmed complete response (CR) or confirmed partial response (PR). The CR was defined as disappearance of all target and non-target lesions and no new lesions. The PR was defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR was defined as 2 CRs or 2 PRs with no evidence of progression in-between. Patients who discontinued randomized treatment without progression, received a subsequent anti-cancer therapy and then responded were not included as responders for ORR.	Up to approximately 26 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall Survival (OS) was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique.	Up to approximately 36 months
Progression-free Survival (PFS)	PFS based on investigator assessments according to RECIST version 1.1 was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (i.e., PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of ≥5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters, or a measurable increase in a non-target lesion, or the appearance of new lesions. Median PFS was calculated using the Kaplan-Meier technique.	Up to approximately 26 months
Number of Participants Who Experience One or More Adverse Events (AE)	An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.	Up to approximately 36 months

Collaborators and Investigators

• Sponsor: West China Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Estimated): September 6, 2026
• Study Completion (Estimated): March 6, 2027

Study Registration Dates

• First Submitted: February 27, 2025
• First Submitted That Met QC Criteria: February 27, 2025
• First Posted (Actual): March 5, 2025

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Lenvatinib; durvalumab; HAIC; locally advanced or metastatic intrahepatic cholangiocarcinoma
• 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; Enzyme Inhibitors; Protein Kinase Inhibitors; durvalumab; lenvatinib
• Other Study ID Numbers: HAIC-quad-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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