Safety and Efficacy of Radiation Plus TACE and Lenvatinib in Advanced HCC With PVTT

Safety and Efficacy of External Beam Radiation Plus Transarterial Chemoembolization and Lenvatinib vs Transarterial Chemoembolization and Lenvatinib in Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

This is a multicentri prospective cohort study to investigate the safety and efficacy of external beam radiation (RT) combined with transarterial chemoembolization (TACE) and lenvatinib vs TACE and lenvatinib in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).

Study Overview

• Status: Withdrawn
• Conditions: Advanced Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Lenvatinib; Procedure: TACE; Radiation: External beam radiation (RT)

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-sen University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. age 18-75 years;
2. histologically or cytologically or clinically confirmed diagnosis of HCC;
3. presenting with PVTT and at least one measurable intrahepatic lesion on the basis of modified Response Evaluation Criteria in Solid Tumors (mRECIST); an intrahepatic lesion consisting of a single tumor (≤ 10.0 cm) or multiple tumors (≤ 3 foci) with the tumor burden < 50%;
4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
5. Child-Pugh class A or B;
6. life expectancy of at least 3 months;
7. satisfactory blood, liver, and kidney function parameters. The acceptable blood, liver, and kidney parameters were (1) neutrophil count ≥ 1.5 × 109/L; (2) platelet count ≥ 60 × 109/L; (3) hemoglobin concentration ≥ 90 g/L; (4) serum albumin concentration ≥ 30 g/L; (5) bilirubin ≤ 50 μmol/L; (6) AST and ALT < 5 × upper limit of normal (ULN) and alkaline phosphatase < 4 × ULN; (7) extended prothrombin time < 6 seconds of ULN; and (8) serum creatinine < 1.5 × ULN.

Exclusion Criteria:

1. history of liver and adjacent tissue radiation;
2. medical history of hepatic decompensation, such as hepatic encephalopathy and esophageal or gastric variceal bleeding;
3. extrahepatic spread;
4. combination with other malignant diseases;
5. contraindications for TACE;
6. pregnant and lactating women;
7. severe dysfunction of the heart, kidney, or other organs;
8. hypersensitivity to intravenous contrast agents;
9. with HIV, syphilis infection;
10. allogeneic organ transplant recipients;
11. suffering from mental and psychological diseases may affect informed consent;
12. unable to take oral medication;
13. active gastric or duodenal ulcers within 3 months before enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RT+TACE+Lenvatinib; Patients in RT+TACE+Lenvatinib group will take oral lenvatinib first and receive TACE one day after oral administration of lenvatinib. RT will begin within 4 weeks after the first TACE.	Drug: Lenvatinib; Lenvatinib will be initially provided to patients first (dose: 8 mg qd for patients < 60 kg, and 12 mg qd for patients ≥ 60 kg); Procedure: TACE; TACE will be performed one day after oral administration of lenvatinib. Either cTACE or DEB-TACE can be used, depending on the condition of each center.; Radiation: External beam radiation (RT); RT will be given within 4 weeks after the first TACE with linear accelerator-based photon beams. Gross tumor volume is defined as intrahepatic tumor and vascular invasion including a 1-cm margin into the contiguous HCC. Prescription dose will be 4500-6000 cGy in 25 fractions.
Active Comparator: TACE+Lenvatinib; Patients in TACE+Lenvatinib group will take oral lenvatinib first and receive TACE one day after oral administration of lenvatinib.	Drug: Lenvatinib; Lenvatinib will be initially provided to patients first (dose: 8 mg qd for patients < 60 kg, and 12 mg qd for patients ≥ 60 kg); Procedure: TACE; TACE will be performed one day after oral administration of lenvatinib. Either cTACE or DEB-TACE can be used, depending on the condition of each center.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from the first day of lenvatinib oral administration to death, regardless of disease recurrence.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the time from the first day of lenvatinib oral administration to progression or death.	Up to 2 years
Objective Response Rate (ORR)	ORR is defined as the percentage of patients who have achieved complete response (CR) or partial response (PR), as measured by modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria.	Up to 2 years
Disease Control Rate (DCR)	DCR is defined as the percentage of patients who have achieved CR, PR or stable disease(SD), as measured by mRECIST criteria.	Up to 2 years
ncidence of Adverse Events (AE)	The percentage of patients who suffer adverse events from the first day of lenvatinib oral administration to last follow-up, assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.	Up to 2 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Publications and helpful links

General Publications

• Abulimiti M, Li Z, Wang H, Apiziaji P, Abulimiti Y, Tan Y. Combination Intensity-Modulated Radiotherapy and Sorafenib Improves Outcomes in Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis. J Oncol. 2021 Dec 3;2021:9943683. doi: 10.1155/2021/9943683. eCollection 2021.
• Yoon SM, Ryoo BY, Lee SJ, Kim JH, Shin JH, An JH, Lee HC, Lim YS. Efficacy and Safety of Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma With Macroscopic Vascular Invasion: A Randomized Clinical Trial. JAMA Oncol. 2018 May 1;4(5):661-669. doi: 10.1001/jamaoncol.2017.5847.
• Peng Z, Fan W, Zhu B, Wang G, Sun J, Xiao C, Huang F, Tang R, Cheng Y, Huang Z, Liang Y, Fan H, Qiao L, Li F, Zhuang W, Peng B, Wang J, Li J, Kuang M. Lenvatinib Combined With Transarterial Chemoembolization as First-Line Treatment for Advanced Hepatocellular Carcinoma: A Phase III, Randomized Clinical Trial (LAUNCH). J Clin Oncol. 2023 Jan 1;41(1):117-127. doi: 10.1200/JCO.22.00392. Epub 2022 Aug 3.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: October 20, 2022
• First Submitted That Met QC Criteria: October 20, 2022
• First Posted (Actual): October 24, 2022

Study Record Updates

• Last Update Posted (Estimate): February 16, 2023
• Last Update Submitted That Met QC Criteria: February 14, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• 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: HCC202211

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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