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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Lenvatinib
* Procedure: TACE
* Radiation: External beam radiation (RT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-75 years; histologically or cytologically or clinically confirmed diagnosis of HCC; 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%; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Child-Pugh class A or B; life expectancy of at least 3 months; 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: history of liver and adjacent tissue radiation; medical history of hepatic decompensation, such as hepatic encephalopathy and esophageal or gastric variceal bleeding; extrahepatic spread; combination with other malignant diseases; contraindications for TACE; pregnant and lactating women; severe dysfunction of the heart, kidney, or other organs; hypersensitivity to intravenous contrast agents; with HIV, syphilis infection; allogeneic organ transplant recipients; suffering from mental and psychological diseases may affect informed consent; unable to take oral medication; active gastric or duodenal ulcers within 3 months before enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RT+TACE+Lenvatinib<br>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<br>* Lenvatinib will be initially provided to patients first (dose: 8 mg qd for patients < 60 kg, and 12 mg qd for patients ≥ 60 kg)<br>Procedure: TACE<br>* 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.<br>Radiation: External beam radiation (RT)<br>* 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.<br>|
| Active Comparator: TACE+Lenvatinib<br>Patients in TACE+Lenvatinib group will take oral lenvatinib first and receive TACE one day after oral administration of lenvatinib. | Drug: Lenvatinib<br>* Lenvatinib will be initially provided to patients first (dose: 8 mg qd for patients < 60 kg, and 12 mg qd for patients ≥ 60 kg)<br>Procedure: TACE<br>* 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.<br>|

What is the study measuring?
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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 |