SBRT Plus Lenvatinib and TACE for Advanced Primary HCC: A Phase 3 Trial (SEARCH)

Advanced Hepatocellular Carcinoma Clinical Trial

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Official title:

Stereotactic Body Radiation Therapy Plus Lenvatinib and Transarterial Chemoembolization for Advanced Primary Hepatocellular Carcinoma: A Phase 3, Multicentric, Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05718232
• Other study ID #: HCC202210
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: March 2023
• Est. completion date: February 2027

Study information

• Verified date: February 2023
• Source: Sun Yat-sen University
• Contact: Ming Kuang, Ph.D.
• Phone: 008687755766
• Email: kuangm[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 3, multicentri, randomised, open label study. The purpose is to investigate the safety and efficacy of stereotactic body radiation therapy (SBRT) combined with transarterial chemoembolization (TACE) and lenvatinib (LEN) in the treatment of advanced hepatocellular carcinoma with portal vein tumor thrombus.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 136
• Est. completion date: February 2027
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age 18-75 years old;

2. Patients with primary advanced HCC (in accordance with AASLD2018 guidelines for the diagnosis of HCC), without any previous treatment;

3. There is at least one measurable lesion in the liver according to mRECIST criteria, single tumor = 10.0 cm or multiple tumors and tumor burden =50% , with portal vein tumor embolus;

4. ECOG score 0-1;

5. Child-Pugh class A;

6. Expected survival time = 3 months;

7. Blood, liver and kidney function meet the following conditions: Neutrophil count = 1.5 × 10 9 /L; Platelet count = 60 × 10 9 /L; Hemoglobin = 90 g/L; Serum albumin = 30 g/L; Bilirubin = 50 umol/L; AST, ALT = 5 times the upper limit of normal, ALP = 4 times the upper limit of normal; Prolongation of prothrombin time not to exceed the upper limit of normal by 6 seconds; Creatinine = 1.5 times the upper limit of normal.

Exclusion Criteria:

1. Extrahepatic metastases;

2. Previous history of liver or adjacent tissue radiation;

3. Previous history of hepatic encephalopathy, refractory ascites or gastric esophageal varices;

4. There are contraindications to TACE treatment, such as portosystemic shunt, liver flow ablation, significant atherosclerosis;

5. Hypersensitivity to intravenous contrast agents;

6. Pregnant or lactating women or subjects with family planning within two years;

7. With HIV, syphilis infection;

8. Accompanied by other malignant tumors or suffering from other malignancies within 5 years before enrollment;

9. Allogeneic organ transplant recipients;

10. Severe dysfunction of heart and kidney or other organs;

11. Active severe infection > grade 2 (NCI-CTC version 5);

12. Suffering from mental and psychological diseases may affect informed consent;

13. Unable to take oral medication;

14. Participated in other drug clinical trials within 12 months before enrollment;

15. Active gastric or duodenal ulcers within 3 months before enrollment.

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• Lenvatinib
Lenvatinib will be taken within 3 days of randomization (dose: 8 mg qd for patients <60kg, and 12 mg qd for patients = 60kg)

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:
• SBRT
SBRT will be given within 3 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 4500-5000 cGy in 5-8 fractions.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS is defined as the time from first treatment to death, regardless of disease recurrence.	Up to 2 years
Secondary	Progression-Free Survival (PFS)	PFS is defined as the time from the first treatment to progression or death.	Up to 2 years
Secondary	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
Secondary	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
Secondary	Incidence of Adverse Events (AE)	Incidence of AE is defined as the percentage of patients who suffer adverse events from the first treatment to last follow-up, assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.	Up to 2 years
Secondary	Time to Progression (TTP)	TTP is defined as the time from the first treatment to progression.	Up to 2 years