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

NCT ID: NCT05718232

Last Updated: 2023-02-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-31
• Study Completion Date: 2027-02-28

Brief 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.

Conditions

Advanced Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

SBRT+TACE+Lenvatinib

Patients in SBRT+TACE+Lenvatinib group will take oral lenvatinib within 3 days of randomization and receive TACE 1 day after oral administration of lenvatinib. SBRT will begin within 3 weeks after the first TACE.

Group Type: EXPERIMENTAL

Lenvatinib

Intervention Type: DRUG

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

TACE

Intervention Type: PROCEDURE

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.

SBRT

Intervention Type: RADIATION

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.

Lenvatinib

Patients in Lenvatinib group will take oral lenvatinib alone.

Group Type: ACTIVE_COMPARATOR

Lenvatinib

Intervention Type: DRUG

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

Interventions

Lenvatinib

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

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

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.

Intervention Type: RADIATION

Eligibility Criteria

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.

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

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Ming Kuang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ming Kuang, Ph.D.

Role: STUDY_CHAIR

First Affiliated Hospital, Sun Yat-Sen University

Locations

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Countries

China

Central Contacts

Ming Kuang, Ph.D.

Role: CONTACT

kuangm@mail.sysu.edu.cn

008687755766 ext. 8576

Facility Contacts

Ming Kuang, Ph.D.

Role: primary

kuangm@mail.sysu.edu.cn

008687755766 ext. 8576

References

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.

Reference Type: BACKGROUND

PMID: 35921605 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34899910 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29543938 (View on PubMed)

Other Identifiers

HCC202210

Identifier Type: -

Identifier Source: org_study_id