HAIC Combine With Lenvatinib and PD-1 Inhibitors for Advanced HCC With PVTT

January 22, 2026 updated by: Xiaodong Wang, MD, Peking University

Hepatic Arterial Infusion Chemotherapy Combine With Lenvatinib and PD-1 Inhibitors for Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis.

The purpose of this study is to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy combined with Lenvatinib and PD-1 inhibitors compared to Lenvatinib plus PD-1 inhibitors for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Hepatic arterial infusion chemotherapy (HAIC) can significantly improve the local drug concentration in liver compared to systemic chemotherapy. The efficacy of HAIC for hepatocellular (HCC), cholangiocarcinoma, gallbladder, and colorectal carcinoma liver metastasis has been proved by many published studies. HAIC with oxaliplatin and 5-fluorouracil could significantly prolong survival time for HCC patients with portal vein tumor thrombosis (PVTT). Lenvatinib, as a new oral anti-neovascularity inhibitor, was proved to have similar efficacy in HCC patients compared to sorafenib in REFLECT study. The sub-group analysis showed that the median overall survival (OS) in Lenvatinib group was significantly longer that sorafenib group in Chinese HCC patients. Recently, the programmed death-1 (PD-1) inhibitors alone or combined with targeted therapy was explored and confirmed to be effective for advanced HCC, with the median progression-free survival (PFS) and median OS of 2.1-5.6 months and 14.4-22.1 months, resepectively. Thus, the investigators carried out this prospective controlled trial to compare the efficacy and safety of HAIC combined with Lenvatinib and PD-1 inhibitors and Lenvatinib and PD-1 inhibitors for advanced HCC with PVTT.

Total 66 subjects will be recruited in this trial, each group of 33 subjects in treatment group (HAIC-Cola group) and control group (Cola group). The primary endpoint is six-month progression-free survival rate, and the secondary endpoints are OS, overall response rate (ORR), PFS, time-to-progression (TTP) and safety. The safety evaluation will be carried out according to the standard of adverse reaction classification (Common Terminology Criteria for Adverse Events, CTCAE v5.0).

Study Type

Interventional

Enrollment (Actual)

66

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100142
        • Peking Univerisity Cancer Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age and gender: >18 years old and≤75 years old, both men and women.
  2. All subjects must have advanced hepatocellular carcinoma with portal vein tumor thrombosis confirmed by pathological or clinical diagnosis.
  3. One measurable lesion at least.
  4. ECOG PS 0-1 before 1 week of treatment begnining.
  5. Child-Pugh class A; ALBI class 1-2.
  6. Systemic-cheomtherapy-naive and HAIC-naive.
  7. BCLC C stage with PVTT (Vp1 - Vp4).
  8. Without distant metastasis.
  9. Patients who are expected to live more than 3 months.
  10. Subjects must volunteer to participate in the study, signed informed consent, and were able to comply with the program requirements of visits and related procedures.

  11. Patients with laboratory values that meet the following criteria:

    1. Hemoglobin≥90 g/L;
    2. Neutrophile granulocytes≥1.5×109/L;
    3. Platelet count≥75×109/L;
    4. Albumin≥30 g/L;
    5. Total serum bilirubin ≤ 2 times upper limits of normal;
    6. AST and ALT ≤ 5 times upper limits of normal;
    7. Serum creatinine ≤ 1.5 times upper limits of normal;
    8. Alkaline phosphatase ≤ 5 times upper limits of normal;
    9. Prothrombin time or international normalized ratio ≤ 1.5 times upper limits of normal, activated partial thromboplastin time (APTT) ≤ 1.5×ULN.

Exclusion Criteria:

  1. Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma confirmed by histology or cytology.
  2. History of malignant tumor, excluding the following cases:
  3. Allergic to contrast agent.
  4. Allergic to oxaliplatin.
  5. History of usage of immune inhibitor drug within 14 days before the injection of PD-1 inhibitors, except nasal spray and inhaled corticosteroids or physiological doses of systemic steroid hormones (no more than 10 mg/day of prednisolone or other corticosteroids with equivalent physiological doses).
  6. Factors influenced oral Lenvatinib, such as inability to swallow, chronic diarrhea and intestinal obstruction, or other conditions that significantly affect the administration and absorption of the drug.
  7. Allergic to Lenvatinib, PD-1 inhibitors, and other mono-colonal antibodies.
  8. Vaccination with live attenuated vaccine within 4 weeks before the first dose or planned during the study period.
  9. Peripheral neuropathy> Grade 1.
  10. History of active autoimmune disease or autoimmune disease.
  11. History of other malignant tumor, except for radically treated basal cell, squamous cell skin cancer, or cervical carcinoma in situ.
  12. History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) .
  13. Clinically significant cardiovascular disease, including, but not limited to, acute myocardial infarction, severe/unstable angina or prior coronary artery bypass surgery, congestive heart failure (NYHA >2), poorly controlled arrhythmias or arrhythmias requiring pacemaker therapy, hypertension not controlled by medication (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) within the past 6 months.
  14. Abnormal coagulation function (INR>1.5 or APTT>1.5×ULN) , have bleeding tendency, or are receiving thrombolytic therapy, anticoagulation therapy or antiplatelet therapy, etc..
  15. History of inherited or acquired bleeding and thrombotic tendency, such as hemophilia, coagulopathy, thrombocytopenia, hypersplenism, etc..
  16. History of significant coughing up blood 2 months before entering the study, or the daily volume of hemoptysis reached 2.5 ml or more.

  17. Patients at risk of gastrointestinal bleeding, including the following:

    1. There are active peptic ulcer lesions.
    2. Those who have a history of melena and hematemesis within 3 months.
    3. For fecal occult blood (+) or (+/-), it is necessary to recheck the stool routine within 1 week. Those who still (+) or (+/-) must undergo gastroscopy. If there is ulcer, bleeding disease, and the treating physician believes that there is a potential risk of bleeding.
  18. History of thrombosis and/or embolism within 6 months of the start of treatment.
  19. Complicated infections requiring drug intervention (such as intravenous infusion of antibiotics, antifungal or antiviral drugs) within 4 weeks before the first treatment, or unexplained fever >38.5°C during the screening period/before the first administration.
  20. Participated in any other clinical research within 4 weeks before the first treatment.
  21. History of psychotropic drug abuse or drug use.
  22. Other serious physical, mental illnesses or laboratory abnormalities, which may increase the risk of participating in the research or interfere with the results of the research, and those who the researcher believes are not suitable for participating in this research.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HAIC-Cola group
Hepatic arterial chemotherapy consisted of infusions of oxaliplatin (35 mg/m2 for 2 hours), followed by 5-fluorouracil (600 mg/m2 for 22 hours) on day1-3 every 4 weeks. 12/8 mg (weight ≥ 60kg / < 60 kg) of Lenvatinib once daily after HAIC. PD-1 inhibitors injection intravenously or percutaneously before 24h of HAIC every 4 week.
Procedure: HAIC
Hepatic arterial chemotherapy consisted of infusions of oxaliplatin (35 mg/m2 for 2 hours), followed by 5-fluorouracil (600 mg/m2 for 22 hours) on day1-3 every 4 weeks.
Drug: Lenvatinib 1
12/8 mg (weight ≥ 60kg / < 60 kg) of Lenvatinib once daily after HAIC.
Drug: PD-1 Inhibitors
PD-1 inhibitors injection intravenously or percutaneously before 24h of HAIC every 4 week.
Other Names:
  • PD-1
Active Comparator: Cola group
12/8 mg (weight ≥ 60kg / < 60 kg) of Lenvatinib once daily. PD-1 inhibitors injection intravenously or percutaneously every 4 week.
Drug: Lenvatinib 2
12/8 mg (weight ≥ 60kg / < 60 kg) of Lenvatinib once daily.
Drug: PD-1 inhibitors 2
PD-1 inhibitors injection intravenously or percutaneously every 4 week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
6-month progression-free survival rate
Time Frame: From the date of treatment begining to the date of 6 months after the treatment begining.
Proportion of patients with 6- month progression-free survival after treatment begining in all patients.
From the date of treatment begining to the date of 6 months after the treatment begining.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: From date of treatment beginning until the date of death from any cause, assessed up to 100 months.
The time from treatment initiation to death due to any cause
From date of treatment beginning until the date of death from any cause, assessed up to 100 months.
Objective survival rate
Time Frame: Evaluation of tumor burden based on mRECIST criteria through study completion, an average of once per 3 months.
The proportion of participants in the analysis population who have complete response (CR) or partial response (PR) determined by investigators using mRECIST criteria at any time during the study.
Evaluation of tumor burden based on mRECIST criteria through study completion, an average of once per 3 months.
Progression-free survival
Time Frame: From date of treatment beginning until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.
The time from treatment initiation to the first documented disease progression or death due to any cause, whichever occurs firstly.
From date of treatment beginning until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.
Time to progression
Time Frame: Evaluation of tumor burden based on mRECIST criteria until first documented progress, assessed up to 100 months.
Time to progression is defined as time from treatment initiation to radiological progression.
Evaluation of tumor burden based on mRECIST criteria until first documented progress, assessed up to 100 months.
Number of patients with treatment-related adverse events
Time Frame: Through study completion, an average of once per 1 month.
Number of patients with AE, treatment-related AE (TRAE), serious adverse event (SAE) assessed by CTCAE v5.0.
Through study completion, an average of once per 1 month.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University

Investigators

  • Study Director: Xiaodong Wang, MD, Peking University Cancer Hospital & Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 10, 2022

Primary Completion (Actual)

December 29, 2023

Study Completion (Actual)

December 28, 2025

Study Registration Dates

First Submitted

November 26, 2021

First Submitted That Met QC Criteria

December 8, 2021

First Posted (Actual)

December 21, 2021

Study Record Updates

Last Update Posted (Actual)

January 23, 2026

Last Update Submitted That Met QC Criteria

January 22, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HAIC-Cola

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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