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

NCT ID: NCT06210334

Last Updated: 2024-02-20

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-31
• Study Completion Date: 2026-01-31

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).

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).

Conditions

Hepatocellular Carcinoma With PVTT

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Tislelizumab

Intervention Type: DRUG

Tislelizumab 200mg, iv, d3, q3w

Lenvatinib

Intervention Type: DRUG

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

Interventions

Tislelizumab

Tislelizumab 200mg, iv, d3, q3w

Intervention Type: DRUG

Lenvatinib

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

Intervention Type: DRUG

Other Intervention Names

PD-1; TKI

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Li Xiao Wei

OTHER

Sponsor Role: lead

Responsible Party

Li Xiao Wei

Associate chief physician

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jian Zhai, MM

Role: STUDY_DIRECTOR

Eastern Hepatobiliary Surgery Hospital

Locations

Eastern Hepatobiliary Surgery Hospital

Yangpu, Shanghai Municipality, China

Countries

China

Central Contacts

Jian Zhai, MM

Role: CONTACT

jianzhai1979@126.com

+862181875172

Xiaowei Li, MM

Role: CONTACT

aass123--@163.com

+862181875173

Facility Contacts

Jian Zhai, MM

Role: primary

jianzhai1979@126.com

+862181875172

Xiaowei Li, MM

Role: backup

aass123--@163.com

+862181875172

References

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Study Documents

Document Type: Clinical Study Report

View Document

Other Identifiers

EasternHSH-IR

Identifier Type: -

Identifier Source: org_study_id