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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05718232

Collaborator

(none)

136

Enrollment

Location

Arms

47.1

Anticipated Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Hepatocellular Carcinoma	Drug: Lenvatinib Procedure: TACE Radiation: SBRT	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

136 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Feb 1, 2027

Anticipated Study Completion Date :

Feb 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	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.
Active Comparator: Lenvatinib Patients in Lenvatinib group will take oral lenvatinib alone.	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)

Arm

Intervention/Treatment

Experimental: 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.

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.

Active Comparator: Lenvatinib

Patients in Lenvatinib group will take oral lenvatinib alone.

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)

Outcome Measures

Primary Outcome Measures

Overall Survival (OS) [Up to 2 years]
OS is defined as the time from first treatment to death, regardless of disease recurrence.

Secondary Outcome Measures

Progression-Free Survival (PFS) [Up to 2 years]
PFS is defined as the time from the first treatment to progression or death.
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.
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.
Incidence of Adverse Events (AE) [Up to 2 years]
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.
Time to Progression （TTP） [Up to 2 years]
TTP is defined as the time from the first treatment to progression.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18-75 years old;
Patients with primary advanced HCC (in accordance with AASLD2018 guidelines for the diagnosis of HCC), without any previous treatment;
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;
ECOG score 0-1;
Child-Pugh class A;
Expected survival time ≥ 3 months;
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:

Extrahepatic metastases;
Previous history of liver or adjacent tissue radiation;
Previous history of hepatic encephalopathy, refractory ascites or gastric esophageal varices;
There are contraindications to TACE treatment, such as portosystemic shunt, liver flow ablation, significant atherosclerosis;
Hypersensitivity to intravenous contrast agents;
Pregnant or lactating women or subjects with family planning within two years;
With HIV, syphilis infection;
Accompanied by other malignant tumors or suffering from other malignancies within 5 years before enrollment;
Allogeneic organ transplant recipients;
Severe dysfunction of heart and kidney or other organs;
Active severe infection > grade 2 (NCI-CTC version 5);
Suffering from mental and psychological diseases may affect informed consent;
Unable to take oral medication;
Participated in other drug clinical trials within 12 months before enrollment;
Active gastric or duodenal ulcers within 3 months before enrollment.