HAIC Combine Tislelizumab and Lenvatinib in the Treatment of HCC With Type IV (Vp4) Portal Vein Tumor Thrombus (HAI-TL) (HAI-TL)

February 17, 2024 updated by: Li Xiao Wei

The Safety and Efficacy of Hepatic Arterial Infusion Chemotherapy (HAIC) Combine Tislelizumab and Lenvatinib in the Treatment of Hepatocellular Carcinoma (HCC) With Type IV(Vp4) Portal Vein Tumor Thrombus (PVTT): A Prospective, Single-armed, Stage II Clinical Trial

To estimate the safety and efficacy of hepatic artery infusion chemotherapy (HAIC) combine Tislelizumab and Lenvatinib (HAI-TIS-LEN) in the Treatment of hepatocellular carcinoma (HCC) with type IV(Vp4) portal vein tumor thrombus (PVTT).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

According to the Chinese guidelines for the diagnosis and treatment of primary liver cancer, patients with hepatocellular carcinoma (HCC) accompanied by portal vein tumor thrombosis (PVTT) are classified as being in an advanced stage (CNLC IIIa). PVTT, particularly the type IV (Vp4), is considered a highly concerning complication of HCC due to its significant morbidity and mortality rates. Furthermore, the absence of effective treatment options contributes to an unfavorable prognosis.

Hepatic arterial infusion chemotherapy (HAIC) delivers chemotherapy drugs directly through a catheter into the nourishing arteries of the tumor, maintaining a high concentration of chemotherapeutic agents within the tumor and tumor thrombus, thereby promoting necrosis. HAIC with modified FOLFOX (oxaliplatin, 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1; and 5-fluorouracil infusion 2400 mg/m2 for 46 h) could significantly prolong survival time for HCC patients with PVTT.

In recent years, official guidelines have approved several immune checkpoint inhibitors for advanced HCC. Lenvatinib, an innovative oral anti-neovascularity inhibitor, has demonstrated comparable efficacy to sorafenib in HCC patients, as evidenced by the REFLECT study. Additionally, the exploration of programmed death-1 (PD-1) inhibitors, either alone or in combination with targeted therapy, has been confirmed as effective for advanced HCC.

Against this background, researchers have initiated a prospective, single-arm, Stage II clinical trial to assess the effectiveness and safety of HAIC combined with Tislelizumab and Lenvatinib (HAI-TIS-LEN) for advanced HCC with Vp4 involvement. A total of 45 subjects will be enrolled in this trial. The primary endpoint of the study is the median overall survival (mOS), the secondary endpoints including the overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), time-to-progression (TTP), and safety assessment. The safety assessment will be conducted in accordance with the standard adverse reaction classification outlined in the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

Study Type

Interventional

Enrollment (Estimated)

54

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 Contact

Study Contact Backup

Study Locations

  • China
    • Shanghai
      • Yangpu, Shanghai, China
        • Eastern Hepatobiliary Surgery Hospital
        • Contact:
        • Contact:

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histologically, cytologically, or clinically confirmed diagnosis of hepatocellular carcinoma (HCC).
  2. Age between 18 and 75 years.
  3. Presence of type 4 portal vein tumor thrombosis (PVTT).
  4. Child-Pugh A or B liver function.
  5. Eastern Cooperative Group performance status (ECOG) score of 0-2.

  6. Satisfactory blood, liver, and kidney function parameters, including:

    • (a) Hemoglobin concentration ≥ 8.5 g/dL, neutrophil count ≥ 1.5 × 10^9/L, platelet count ≥ 40 × 10^9/L.
    • (b) Serum albumin concentration ≥ 30 g/L, bilirubin ≤ 50 μmol/L, AST and ALT < 5 × upper limit of normal (ULN), and alkaline phosphatase < 4 × ULN.
    • (c) Extended prothrombin time < 6 seconds of ULN.
    • (d) Serum creatinine < 1.5 × ULN.
  7. Ability to comprehend the protocol and provide informed consent by signing a written document.

Exclusion Criteria:

  1. History of a second primary malignant tumor.
  2. Severe dysfunction of the heart, kidneys, or other organs.
  3. Evidence of hepatic decompensation, including ascites, active gastrointestinal bleeding, or hepatic encephalopathy.
  4. Pregnancy or lactation.
  5. Known history of HIV.
  6. History of organ allograft.
  7. Known or suspected allergy to investigational agents or any agent administered in conjunction with this trial.
  8. Active gastric or duodenal ulcers within 3 months before enrollment.
  9. Incomplete medical data or loss to follow-up.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HAIC combined with Tislelizumab and Lenvatinib (HAI-TIS-LEN) group
HAIC with modified FOLFOX (oxaliplatin, 85 mg/ m2, leucovorin 400 mg/ m2, 5-fluorouracil bolus 400 mg/m2 on day 1; and 5-fluorouracil infusion 2400 mg/ m2 for 46 h) on day1-2 every 3 weeks. Tislelizumab injection intravenously after 24h of HAIC every 3 week. Lenvatinib 12/8 mg (weight ≥ 60 kg/< 60 kg) orally once daily starting 1-3 days after HAIC.
Drug: Tislelizumab
Tislelizumab 200mg, iv, d3, q3w
Other Names:
  • PD-1
Drug: Lenvatinib
Lenvatinib 8mg (<60kg) or 12mg (≥60kg), po, qd
Other Names:
  • TKI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From the date of treatment initiation until the date of death from any cause, assessed up to 60 months.
Duration from the date of initial HAI-TIS-LEN treatment to the date of death due to any cause.
From the date of treatment initiation until the date of death from any cause, assessed up to 60 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: The average expectation is 36 months.
Defined as the time from the treatment initiation to the date of the first objectively documented tumor progression or death, whichever occurs first, assessed by IRC and investigators, respectively, per RECIST v 1.1 and mRECIST.
The average expectation is 36 months.
Time-to-progression (TTP)
Time Frame: The average expectation is 36 months.
Defined as the time from treatment initiation to radiological progression.
The average expectation is 36 months.
Objective Response Rate (ORR)
Time Frame: On average once every month, assessed up to 36 months.
Defined as the proportion of participants in the study population who achieve a complete response (CR) or partial response (PR), as determined by investigators using the RECIST v 1.1 and mRECIST criteria, at any time during the study.
On average once every month, assessed up to 36 months.
Disease Control Rate (DCR)
Time Frame: On average once every month, assessed up to 36 months.
Defined as the proportion of patients whose best overall response is CR, PR, or SD, assessed by investigators, per RECIST v 1.1 and mRECIST
On average once every month, assessed up to 36 months.
Adverse Events (AE)
Time Frame: From the date of treatment initiation until 60 days after the last treatment.
Any adverse events related to treatment drugs, including details such as adverse event type, frequency, and severity.
From the date of treatment initiation until 60 days after the last treatment.

Collaborators and Investigators

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

Sponsor

Li Xiao Wei

Investigators

  • Study Director: Jian Zhai, MM, Eastern Hepatobiliary Surgery Hospital

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 (Estimated)

March 1, 2024

Primary Completion (Estimated)

July 1, 2025

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

January 2, 2024

First Submitted That Met QC Criteria

January 15, 2024

First Posted (Actual)

January 18, 2024

Study Record Updates

Last Update Posted (Actual)

February 20, 2024

Last Update Submitted That Met QC Criteria

February 17, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EasternHSH-IR

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The data that support the findings of this study will be openly available in Research Data Deposit at https://www.researchdata.org.cn, after publication.

IPD Sharing Time Frame

Submission of data starting 6 months after publication, expected to be open for 6 months.

IPD Sharing Access Criteria

open

IPD Sharing Supporting Information Type

  • CSR

Study Data/Documents

  1. Clinical Study Report

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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