Lenvatinib Combined With TACE and Camrelizumab in Conversion Resection for Advanced Hepatocellular Carcinoma (LEN-TAC Study)

Lenvatinib Combined With Transcatheter Arterial Chemoembolization and Camrelizumab Versus Lenvatinib Combined With Transcatheter Arterial Chemoembolization in Conversion Resection for Advanced Hepatocellular Carcinoma:A Randomized, Open-label, Parallel-controlled, Phase III Study(LEN-TAC Study)

Compared to systemic therapy alone, conversion therapy is promising to improve the prognosis of patients with advanced hepatocellular carcinoma (HCC). Triple therapy (lenvatinib combined with transcatheter arterial chemoembolization and camrelizumab) may have significant efficacy in conversion therapy for patients with advanced HCC, but its safety and efficacy remain unknown. To address this, we have designed a randomized, open-label, parallel-controlled trial to evaluate the safety and efficacy of lenvatinib combined with transcatheter arterial chemoembolization and camrelizumab versus lenvatinib combined with transcatheter arterial chemoembolization in conversion resection for advanced HCC. Totally 196 patients with BCLC C stage HCC will be rigorously screened and included, and the primary endpoints of the study are overall survival. This study aims to provide valuable insights into new treatment strategies for advanced HCC.

Study Overview

• Status: Recruiting
• Conditions: Advanced Hepatocellular Carcinoma
• Intervention / Treatment: Combination product: Lenvatinib combined with TACE and Camrelizumab

• Study Type: Interventional
• Enrollment (Estimated): 196
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tianfu Wen, Professor; Phone Number: 86-18980601471; Email: wentianfu@scu.edu.cn

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Recruiting
      • Huaxi Hospital
      • Contact: Tianfu Wen, Professor; Phone Number: 86-18980601471; Email: wentianfu@scu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged between 18 and 75 years.
2. Patients with HCC who strictly meet the criteria outlined in the Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2022Edition), or those diagnosed by histopathology or cytology.
3. No prior anticancer therapy for HCC(Excluding patients who have received two or fewer TACE treatments).
4. ECOG PS score of 0-1.
5. Child-Pugh class A to B.
6. BCLC stage C Patients: tumor localized in one half of the liver with portal vein tumor thrombus (Vp1-Vp4 patients without contralateral portal vein tumor thrombus).
7. At least one radiographically measurable lesion according to mRECIST.
8. For HBsAg-positive patients, HBV-DNA < 2000 IU/ml (10^4 copies/ml) when undergoing PD-1 monoclonal antibody treatment; HCV RNA negative when HCV antibody is positive.
9. Adequate organ function based on laboratory test results.
10. Adequate blood pressure control with up to 3 antihypertensive agents, defined as BP ≤ 150/90 mmHg at screening with no changes in antihypertensive therapy within 1 week prior to Cycle 1/Day 1.
11. Patients expected to survive more than 3 months.
12. Not planning to become pregnant.

Exclusion Criteria:

1. Known intrahepatic cholangiocarcinoma, sarcomatoid HCC, mixed hepatocellular carcinoma, and fibrolamellar cell carcinoma.
2. Extrahepatic metastasis of HCC.
3. Diffuse HCC or intrahepatic tumor burden ≥ 50% (including contralateral portal vein tumor thrombus, superior mesenteric vein tumor thrombus, and inferior vena cava tumor thrombus).
4. Contraindications to TACE or epirubicin.
5. Known hypersensitivity to lenvatinib ingredients.
6. Known hypersensitivity to the active ingredient or excipients of Camrelizumab.
7. Presence of other malignancies.
8. Pregnancy, lactation, or unwillingness to use effective contraceptive measures.
9. Class II or higher myocardial ischemia or infarction, poorly controlled arrhythmia, cardiac insufficiency class III-IV, or LVEF < 50%.
10. Abnormal coagulation function or bleeding tendency.
11. History of psychiatric disorders or substance abuse.
12. HIV infection.
13. Allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
14. Active infection.
15. Poor compliance such as floating population.
16. Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents.
17. Active autoimmune disease requiring systemic therapy within 2 years prior to the first dose.
18. Systemic glucocorticoid or immunosuppressive therapy within 7 days prior to the first dose.
19. Clinically uncontrolled pleural/peritoneal effusion.
20. Active chronic hepatitis B or C.
21. Vaccination with live vaccines within 30 days prior to the first dose.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lenvatinib combined with TACE and camrelizumab	Combination product: Lenvatinib combined with TACE and Camrelizumab; Once subjects have signed the informed consent and passed screening, they will be randomized in a 1:1 ratio to either the experimental arm (lenvatinib combined with TACE and camrelizumab) or the control arm (lenvatinib combined with TACE).
Active Comparator: lenvatinib combined with TACE	Combination product: Lenvatinib combined with TACE and Camrelizumab; Once subjects have signed the informed consent and passed screening, they will be randomized in a 1:1 ratio to either the experimental arm (lenvatinib combined with TACE and camrelizumab) or the control arm (lenvatinib combined with TACE).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from randomization to death (any cause).	3-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conversional resection rate	conversional resection patients/enrolled patients	2 years
Overall survival at 2 years	The time from start of treatment until death from any cause or the end of the study (the last enrolled patient should be followed for at least 2 years	2 years
Adverse events	The occurrence of any hematological or non-hematological toxicity event (≥ class Ⅲ), including but not limited to impaired liver function, impaired hematological system, hypertension, diarrhea, proteinuria, hand-foot syndrome, etc. Severity of adverse events will be graded according to CTCAE v5.0.	2 years
Objective response rate	The percentage of patients achieving complete response and partial response among all patients. Response to treatment will be evaluated according to mRECIST.	2 years
Disease control rate	The percentage of patients with complete response, partial response and stable disease among all patients.	2 years
Event-free survival	Time from randomization to disease progression, local recurrence, distant metastasis, or death, whichever occurs first, assessed by mRECIST	2 years

Collaborators and Investigators

• Sponsor: Wen Tianfu

Study record dates

Study Major Dates

• Study Start (Estimated): May 10, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: February 12, 2023
• First Submitted That Met QC Criteria: February 12, 2023
• First Posted (Actual): February 22, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Lenvatinib; Camrelizumab; Transcatheter arterial chemoembolization; Advanced hepatocellular carcinoma; Conversion resection
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: HX-IRB-AF-03-V1.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No