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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

• Overall Survival (OS) [Срок оценки: Up to 2 years]

Вторичные конечные точки (5)

• Progression-Free Survival (PFS) [Срок оценки: Up to 2 years]
• Objective Response Rate (ORR) [Срок оценки: Up to 2 years]
• Disease Control Rate (DCR) [Срок оценки: Up to 2 years]
• Incidence of Adverse Events (AE) [Срок оценки: Up to 2 years]
• Time to Progression （TTP） [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Sun Yat-sen University — Гуанчжоу

Публикации

• 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 PMID 35921605
• 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. PMID 34899910
• 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. PMID 29543938

Идентификаторы

NCT: NCT05718232 · HCC202210

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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