Clinical trial NCT03905967: TACE With Lenvatinib Versus Lenvatinib Alone in in First-line Treatment of Advanced HCC
Official title: Transarterial Chemoembolization With Lenvatinib Versus Lenvatinib Alone in First-line Treatment of Advanced Hepatocellular Carcinoma: a Phase III, Multicenter, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Advanced Hepatocellular Carcinoma
Keywords: Lenvatinib
Transarterial chemoembolisation
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2019-04-08
Enrollment: 336
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is is an open label, multicenter, randomized controlled phase 3 clinical trial. The purpose is to compare the efficacy and safety of lenvatinib plus TACE with lenvatinib alone for advanced HCC patients.


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 or with extrahepatic metastasis;
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. Preoperative imaging examination revealed diffuse intrahepatic lesions or invasion, inferior vena cava or primary branch bile duct;
2. Previous history of hepatic encephalopathy, refractory ascites or gastric esophageal varices;
3. There are contraindications to TACE treatment, such as portosystemic shunt, liver flow ablation, significant atherosclerosis;
4. Brain metastases;
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 4);
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;

Primary outcomes:
measure: Overall survival
timeFrame: two years
Secondary outcomes:
measure: Time to progression
timeFrame: two years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Ming Kuang, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.
citation: Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018 Mar 31;391(10127):1301-1314. doi: 10.1016/S0140-6736(18)30010-2. Epub 2018 Jan 5.
citation: Meyer T, Fox R, Ma YT, Ross PJ, James MW, Sturgess R, Stubbs C, Stocken DD, Wall L, Watkinson A, Hacking N, Evans TRJ, Collins P, Hubner RA, Cunningham D, Primrose JN, Johnson PJ, Palmer DH. Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Aug;2(8):565-575. doi: 10.1016/S2468-1253(17)30156-5. Epub 2017 Jun 23.
citation: Park JW, Kim YJ, Kim DY, Bae SH, Paik SW, Lee YJ, Kim HY, Lee HC, Han SY, Cheong JY, Kwon OS, Yeon JE, Kim BH, Hwang J. Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase III STAH trial. J Hepatol. 2019 Apr;70(4):684-691. doi: 10.1016/j.jhep.2018.11.029. Epub 2018 Dec 6.