Clinical trial NCT05280444: Lipiodol-TACE With Idarubicin for Hepatocellular Carcinoma
Official title: Transarterial Chemoembolization With Lipiodol-Idarubicin Emulsion in the Treatment of Hepatocellular Carcinoma: a Prospective, Multicenter, Real-world Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular carcinoma
Transarterial chemoembolization
Idarubicin
Real-world study
Lead sponsor: Zhongda Hospital
Sponsor class: OTHER
First posted: 2022-03-15
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this real-world study is to evaluate the safety and efficacy of lipiodol-TACE with idarubicin for hepatocellular carcinoma.

Detailed description: Idarubicin is a DNA topoisomerase II inhibitor that promotes DNA strand breakage, trapping cells in the G2 phase of the cell cycle and inducing DNA cleavage and cell apoptosis. At the same time, it can be inserted between the DNA base pairs and produce free radicals, thus breaking the DNA double helix structure and inhibiting the extension, replication and transcription of DNA strands. Preclinical studies have shown that idarubicin has higher antitumor activity than epirubicin, especially against SUN-449 human hepatoma cells. In recent years, domestic and foreign scholars have conducted a series of explorations in the treatment of hepatocellular carcinoma with lipiodol-idarubicin emulsion, and have obtained positive results. This proepective， multicenter real-worldstudy aims to evaluate the efficacy and safety of lipiodol-TACE with idarubicin in Chinese HCC patients.

Eligibility criteria: Inclusion Criteria:

1).18-75 years old; no gender limit; 2).Confirmed diagnosis of HCC according to histopathology or CNLC guidelines (2019 Edition); 3）Life expectancy≥3 months; 4).Child-Pugh class A or B; 5).ECOG PS of 0 or 1;6).One of the following cases: CNLC stage IIb and IIIa; CNLC stage Ib and IIa patient who is unable or unwilling to receive surgical treatment due to other reasons (such as advanced age, severe liver cirrhosis, etc.); The main portal vein has not been completely obstructed, with abundant collateral vessels, or restore the blood flow by portal vein stent placement; 7). At least one measurable lesion (the length diameter≥10mm); 8).Laboratory indices: WBC≥3.0×109/L; PLT≥50×109/L; Hb≥70g/L; Cr≤1.5×UNL(upper limit of normal); BIL≤2.0×UNL, ALT≤5.0×UNL, AST≤5.0×UNL.

Exclusion Criteria:

1).The coagulation function is severely decreased and cannot be recovered; 2).The main portal vein is completely embolized by cancer embolism, with few collateral vessels; 3).With active hepatitis or severe infection that cannot be treated at the same time; 4). With cachexia or multiple organ failure; 5). With uncontrollable neurological and mental disorders, or poor compliance; 6.) Primary brain tumors or central nervous system metastasis has not been controlled, with obvious intracranial hypertension or neuropsychiatric symptoms; 7). Pregnant or breast feeding women; 8). Received drug treatments in other clinical trial in the past 4 weeks; 9). Other situations where the investigators judge that the patient should not participate in.

Primary outcomes:
measure: Objective Response Rate(ORR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Disease Control Rate(DCR)
timeFrame: Up to approximately 2 years
measure: Time to Progression(TTP)
timeFrame: Up to approximately 2 years
measure: Overall Survival(OS)
timeFrame: Up to approximately 2 years
measure: Survival Rate
timeFrame: Up to approximately 2 years
measure: Adverse Events(AEs)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Zhongda Hospital, Southeast University
state: Jiangsu
Study officials:
affiliation: Zhongda hospital, Southeast university, Nanjing, China
name: Gao-Jun Teng, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tang A, Hallouch O, Chernyak V, Kamaya A, Sirlin CB. Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis. Abdom Radiol (NY). 2018 Jan;43(1):13-25. doi: 10.1007/s00261-017-1209-1.
citation: Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: clinical frontiers and perspectives. Gut. 2014 May;63(5):844-55. doi: 10.1136/gutjnl-2013-306627. Epub 2014 Feb 14.
citation: Lencioni R, de Baere T, Soulen MC, Rilling WS, Geschwind JF. Lipiodol transarterial chemoembolization for hepatocellular carcinoma: A systematic review of efficacy and safety data. Hepatology. 2016 Jul;64(1):106-16. doi: 10.1002/hep.28453. Epub 2016 Mar 7.
citation: Pelletier G, Ducreux M, Gay F, Luboinski M, Hagege H, Dao T, Van Steenbergen W, Buffet C, Rougier P, Adler M, Pignon JP, Roche A. Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial. Groupe CHC. J Hepatol. 1998 Jul;29(1):129-34. doi: 10.1016/s0168-8278(98)80187-6.
citation: Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002 May;35(5):1164-71. doi: 10.1053/jhep.2002.33156.
citation: Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Sola R, Rodes J, Bruix J; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002 May 18;359(9319):1734-9. doi: 10.1016/S0140-6736(02)08649-X.
citation: Camma C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F, Andreone P, Craxi A, Cottone M. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology. 2002 Jul;224(1):47-54. doi: 10.1148/radiol.2241011262.
citation: Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology. 2003 Feb;37(2):429-42. doi: 10.1053/jhep.2003.50047.
citation: Boulin M, Guiu S, Chauffert B, Aho S, Cercueil JP, Ghiringhelli F, Krause D, Fagnoni P, Hillon P, Bedenne L, Guiu B. Screening of anticancer drugs for chemoembolization of hepatocellular carcinoma. Anticancer Drugs. 2011 Sep;22(8):741-8. doi: 10.1097/CAD.0b013e328346a0c5.
citation: Favelier S, Boulin M, Hamza S, Cercueil JP, Cherblanc V, Lepage C, Hillon P, Chauffert B, Krause D, Guiu B. Lipiodol trans-arterial chemoembolization of hepatocellular carcinoma with idarubicin: first experience. Cardiovasc Intervent Radiol. 2013 Aug;36(4):1039-46. doi: 10.1007/s00270-012-0532-8. Epub 2012 Dec 8.
citation: Tavernier J, Fagnoni P, Chabrot P, Guiu B, Vadot L, Aho S, Boyer L, Abergel A, Hillon P, Sautou V, Boulin M. Comparison of two transarterial chemoembolization strategies for hepatocellular carcinoma. Anticancer Res. 2014 Dec;34(12):7247-53.
citation: Boulin M, Schmitt A, Delhom E, Cercueil JP, Wendremaire M, Imbs DC, Fohlen A, Panaro F, Herrero A, Denys A, Guiu B. Improved stability of lipiodol-drug emulsion for transarterial chemoembolisation of hepatocellular carcinoma results in improved pharmacokinetic profile: Proof of concept using idarubicin. Eur Radiol. 2016 Feb;26(2):601-9. doi: 10.1007/s00330-015-3855-4. Epub 2015 Jun 11.
citation: Guiu B, Jouve JL, Schmitt A, Minello A, Bonnetain F, Cassinotto C, Piron L, Cercueil JP, Loffroy R, Latournerie M, Wendremaire M, Lepage C, Boulin M. Intra-arterial idarubicin_lipiodol without embolisation in hepatocellular carcinoma: The LIDA-B phase I trial. J Hepatol. 2018 Jun;68(6):1163-1171. doi: 10.1016/j.jhep.2018.01.022. Epub 2018 Feb 8.