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

Hepatocellular Carcinoma With PVTT Clinical Trial

— HAI-TL  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06210334
• Other study ID #: EasternHSH-IR
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 2024
• Est. completion date: January 2026

Study information

• Verified date: February 2024
• Source: Eastern Hepatobiliary Surgery Hospital
• Contact: Jian Zhai, MM
• Phone: +862181875172
• Email: jianzhai1979[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 54
• Est. completion date: January 2026
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma With PVTT
• Thrombosis

Intervention

Drug:
• Tislelizumab
Tislelizumab 200mg, iv, d3, q3w
• Lenvatinib
Lenvatinib 8mg (<60kg) or 12mg (=60kg), po, qd

Locations

Country	Name	City	State
China	Eastern Hepatobiliary Surgery Hospital	Yangpu	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Li Xiao Wei

Country where clinical trial is conducted

China, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Lancet Oncol. 2021 Aug;22(8):e347. — View Citation

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. Erratum In: J Clin Oncol. 2010 Dec 20;28(36):5350. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression-free survival (PFS)	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.
Secondary	Time-to-progression (TTP)	Defined as the time from treatment initiation to radiological progression.	The average expectation is 36 months.
Secondary	Objective Response Rate (ORR)	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.
Secondary	Disease Control Rate (DCR)	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.
Secondary	Adverse Events (AE)	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.