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

NCT06210334 | Not Yet Recruiting Phase 2

• 1 other identifier: EasternHSH-IR
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Hepatocellular Carcinoma With PVTT

Keywords

Hepatocellular Carcinoma; Hepatic Arterial Infusion Chemotherapy; Portal Vein Tumor Thrombus; Tislelizumab; Lenvatinib

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  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 Outcomes (5)

• Progression-free survival (PFS)

  The average expectation is 36 months.

• Time-to-progression (TTP)

  The average expectation is 36 months.

• Objective Response Rate (ORR)

  On average once every month, assessed up to 36 months.

• Disease Control Rate (DCR)

  On average once every month, assessed up to 36 months.

• Adverse Events (AE)

  From the date of treatment initiation until 60 days after the last treatment.

Study Arms (1)

HAIC combined with Tislelizumab and Lenvatinib (HAI-TIS-LEN) group

EXPERIMENTAL

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; Drug: Lenvatinib

Interventions

Tislelizumab DRUG

Tislelizumab 200mg, iv, d3, q3w

Also known as: PD-1

HAIC combined with Tislelizumab and Lenvatinib (HAI-TIS-LEN) group

Lenvatinib DRUG

Lenvatinib 8mg (\<60kg) or 12mg (≥60kg), po, qd

Also known as: TKI

HAIC combined with Tislelizumab and Lenvatinib (HAI-TIS-LEN) group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically, cytologically, or clinically confirmed diagnosis of hepatocellular carcinoma (HCC).
• Age between 18 and 75 years.
• Presence of type 4 portal vein tumor thrombosis (PVTT).
• Child-Pugh A or B liver function.
• Eastern Cooperative Group performance status (ECOG) score of 0-2.
• 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.
• Ability to comprehend the protocol and provide informed consent by signing a written document.

You may not qualify if:

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

Sponsors & Collaborators

• Li Xiao Wei: lead

Study Sites (1)

Eastern Hepatobiliary Surgery Hospital

Yangpu, Shanghai Municipality, China

Location

Related Publications (6)

• Zhou J, Sun H, Wang Z, Cong W, Zeng M, Zhou W, Bie P, Liu L, Wen T, Kuang M, Han G, Yan Z, Wang M, Liu R, Lu L, Ren Z, Zeng Z, Liang P, Liang C, Chen M, Yan F, Wang W, Hou J, Ji Y, Yun J, Bai X, Cai D, Chen W, Chen Y, Cheng W, Cheng S, Dai C, Guo W, Guo Y, Hua B, Huang X, Jia W, Li Q, Li T, Li X, Li Y, Li Y, Liang J, Ling C, Liu T, Liu X, Lu S, Lv G, Mao Y, Meng Z, Peng T, Ren W, Shi H, Shi G, Shi M, Song T, Tao K, Wang J, Wang K, Wang L, Wang W, Wang X, Wang Z, Xiang B, Xing B, Xu J, Yang J, Yang J, Yang Y, Yang Y, Ye S, Yin Z, Zeng Y, Zhang B, Zhang B, Zhang L, Zhang S, Zhang T, Zhang Y, Zhao M, Zhao Y, Zheng H, Zhou L, Zhu J, Zhu K, Liu R, Shi Y, Xiao Y, Zhang L, Yang C, Wu Z, Dai Z, Chen M, Cai J, Wang W, Cai X, Li Q, Shen F, Qin S, Teng G, Dong J, Fan J. Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition). Liver Cancer. 2023 Apr 5;12(5):405-444. doi: 10.1159/000530495. eCollection 2023 Oct.

  PMID: 37901768 BACKGROUND

• Thomas MB, Jaffe D, Choti MM, Belghiti J, Curley S, Fong Y, Gores G, Kerlan R, Merle P, O'Neil B, Poon R, Schwartz L, Tepper J, Yao F, Haller D, Mooney M, Venook A. Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol. 2010 Sep 1;28(25):3994-4005. doi: 10.1200/JCO.2010.28.7805. Epub 2010 Aug 2.

  PMID: 20679622 BACKGROUND

• Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.

  PMID: 32402160 BACKGROUND

• Ren Z, Xu J, Bai Y, Xu A, Cang S, Du C, Li Q, Lu Y, Chen Y, Guo Y, Chen Z, Liu B, Jia W, Wu J, Wang J, Shao G, Zhang B, Shan Y, Meng Z, Wu J, Gu S, Yang W, Liu C, Shi X, Gao Z, Yin T, Cui J, Huang M, Xing B, Mao Y, Teng G, Qin Y, Wang J, Xia F, Yin G, Yang Y, Chen M, Wang Y, Zhou H, Fan J; ORIENT-32 study group. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol. 2021 Jul;22(7):977-990. doi: 10.1016/S1470-2045(21)00252-7. Epub 2021 Jun 15.

  PMID: 34143971 BACKGROUND

• Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.

  PMID: 18650514 BACKGROUND

• Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.

  PMID: 29433850 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

tislelizumab; lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Jian Zhai, MM

  Eastern Hepatobiliary Surgery Hospital

  STUDY DIRECTOR

Central Study Contacts

Jian Zhai, MM

CONTACT

+862181875172; jianzhai1979@126.com

Xiaowei Li, MM

CONTACT

+862181875173; aass123--@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate chief physician

Model Details: A Prospective, Single-armed, Stage II Clinical Trial

Study Record Dates

• First Submitted: January 2, 2024
• First Posted: January 18, 2024
• Study Start: March 1, 2024
• Primary Completion: July 1, 2025
• Study Completion: January 1, 2026
• Last Updated: February 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Submission of data starting 6 months after publication, expected to be open for 6 months.
• Access Criteria: open

Locations

CN (1)