HAIC in Combination With PD-1 Inhibitors and Lenvatinib for High Tumor Burden Advanced HCC (CHANCE2416)

Hepatic Arterial Infusion Chemotherapy Plus Lenvatinib and PD-1 Inhibitors Versus Lenvatinib Plus PD-1 Inhibitors as First-line Treatment for High Tumor Burden Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: a Target Trial Emulation Study

The purpose of this study is to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) in combination with PD-1 inhibitors and Lenvatinib in patients with high tumor burden advanced-stage hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).

Study Overview

• Status: Completed
• Conditions: BCLC Stage C Hepatocellular Carcinoma; Lenvatinib; HCC - Hepatocellular Carcinoma; PD-1 Inhibitors; Hepatic Arterial Infusion Chemotherapy
• Intervention / Treatment: Procedure: hepatic artery infusion chemotherapy; Drug: Lenvatinib + PD-1 monoclonal antibody

• Study Type: Observational
• Enrollment (Actual): 244

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110000
      • The First Hospital of China Medical University

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Patients with high tumor burden advanced HCC with PVTT who received HAIC in combination with PD-1 inhibitors and Lenvatinib under real-world practice conditions.

Description

Inclusion Criteria:

1. Age 18 to 80 years old;
2. Diagnosis of HCC was confirmed by histologic or cytologic analysis or clinical features according to the American Association for the Study of Liver Diseases (AASLD) guideline;
3. At least one measurable intrahepatic lesion as per the RECIST 1.1 criteria;
4. HCC staging of the patients are consistent with both the BCLC stage C and the CNLC stage IIIa.
5. Presence of PVTT;
6. Patients received a first-line lenvatinib+PD-1 (L+P) inhibitors combination or that of HAIC+lenvatinib+PD-1 inhibitors (H+L+P). More specifically, the administration of lenvatinib was concomitant with PD-1 inhibitors, and HAIC was performed either concurrently with, or up to 2 months before or after the L+P inhibitors combination therapy. Patients in the H+L+P group should undergo at least 2 cycles of HAIC, receive at least 2 cycles of PD-1 inhibiors and take at least 2 months of lenvatinib. Patients in the L+P group should receive at least 2 cycles of PD-1 inhibiors, and take at least 2 months of lenvatinib.
7. Child-Pugh class A or B7;
8. Tumor burden meets up to 7 out criteria.

Exclusion Criteria:

1. Patients who took anti-tumor treatments before the combination therapy;
2. With other malignant tumors;
3. incomplete data.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HAIC plus Lenvatinib and PD-1 inhibitors; Each patient should receive at least 2 cycles of HAIC, 2 cycles of PD-1inhibitors and take at least 2 months of Lenvatinib. The interval between HAIC and Lenvatinib plus PD-1 inhibitors should be within 2 months.	Procedure: hepatic artery infusion chemotherapy; Hepatic arterial infusion chemotherapy including FOLFOX and RALOX; Drug: Lenvatinib + PD-1 monoclonal antibody; PD-1 inhibitors including Camrelizumab, Sintilimab, Tislelizumab
Lenvatinib plus PD-1 inhibitors; Each patient should receive at least 2 cycles of PD-1 inhibitors and 2 months of Lenvatinib.	Drug: Lenvatinib + PD-1 monoclonal antibody; PD-1 inhibitors including Camrelizumab, Sintilimab, Tislelizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	The OS is defined as the time from the initiation of any combination treatment to death due to any cause.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate(ORR) per RESCIST 1.1	The ORR is defined as the proportion of patients with a documented complete response(CR) or partial response(PR) per RECIST 1.1.	Up to approximately 2 years
ORR of PVTT	The ORR is defined as the proportion of patients with a documented CR or PR of PVTT.	Up to approximately 2 years
Adverse event(AE) per Common Terminology Criteria for Adverse Events(CTCAE) 5.0	The percentage and degree of patients who experience at least one AE, whether or not considered related to the treatment, according to CTCAE version 5.0.	Up to approximately 2 years
Progression free survival(PFS) (Overall)	The PFS is defined as the time from the initiation of any combination treatment to the first documented progressive disease (according to mRECIST) or death due to any cause, whichever occurs first.	Up to approximately 2 years
Progression free survival(PFS) of intra-hepatic lesions	The PFS is defined as the time from the initiation of any combination treatment to the first documented progressive disease of intra-hepatic lesions or death due to any cause, whichever occurs first.	Up to approximately 2 years
Progression free survival(PFS) of extra-hepatic lesions	The PFS is defined as the time from the initiation of any combination treatment to the first documented appearance of extra-hepatic lesions or death due to any cause, whichever occurs first.	Up to approximately 2 years
Progression free survival(PFS) of portal vein tumor thrombus (PVTT)	The PFS is defined as the time from the initiation of any combination treatment to the first documented progressive disease of PVTT or death due to any cause, whichever occurs first.	Up to approximately 2 years
ORR per mRECIST	The ORR is defined as the proportion of patients with a documented CR or PR per mRECIST.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: First Hospital of China Medical University
• Investigators: Principal Investigator: Haibo Shao, First Hospital of China Medical University

Publications and helpful links

General Publications

• Liu J, Zhang S, Shao H. Hepatic arterial infusion chemotherapy plus lenvatinib and PD-1 inhibitors versus lenvatinib plus PD-1 inhibitors as first-line treatment for hepatocellular carcinoma with high tumour burden and portal vein tumour thrombus (CHANCE 2416): study protocol of a multicentre, retrospective, target trial emulation design. BMJ Open. 2025 Sep 9;15(9):e099510. doi: 10.1136/bmjopen-2025-099510.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): October 22, 2025
• Study Completion (Actual): October 22, 2025

Study Registration Dates

• First Submitted: October 5, 2024
• First Submitted That Met QC Criteria: October 5, 2024
• First Posted (Actual): October 8, 2024

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 25, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; lenvatinib
• Other Study ID Numbers: CHANCE2416

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