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

• Sponsor: Sun Yat-sen University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05592197
• Collaborator: (none)
• Enrollment: 100
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 53
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Advanced Hepatocellular Carcinoma	Drug: Lenvatinib; Procedure: TACE; Radiation: External beam radiation (RT)	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 100 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Oct 1, 2018
• Anticipated Primary Completion Date: Mar 1, 2023
• Anticipated Study Completion Date: Mar 1, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [Up to 2 years]

   OS is defined as the time from the first day of lenvatinib oral administration to death, regardless of disease recurrence.

Secondary Outcome Measures

1. Progression-Free Survival (PFS) [Up to 2 years]

   PFS is defined as the time from the first day of lenvatinib oral administration to progression or death.

2. Objective Response Rate (ORR) [Up to 2 years]

   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.

3. Disease Control Rate (DCR) [Up to 2 years]

   DCR is defined as the percentage of patients who have achieved CR, PR or stable disease(SD), as measured by mRECIST criteria.

4. ncidence of Adverse Events (AE) [Up to 2 years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong	China	510080

Sponsors and Collaborators

• Sun Yat-sen University

Investigators

• Study Chair: Ming Kuang, Ph.D., First Affiliated Hospital, Sun Yat-Sen University

Study Documents (Full-Text)

None provided.

More Information

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.
• 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.
• 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.

• Responsible Party: Ming Kuang, Professor, Sun Yat-sen University
• ClinicalTrials.gov Identifier: NCT05592197
• Other Study ID Numbers: HCC202211
• First Posted: Oct 24, 2022
• Last Update Posted: Oct 24, 2022
• Last Verified: Oct 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Lenvatinib

Study Results

No Results Posted as of Oct 24, 2022