Treatment of Cirrhosis-related Hepatocellular Carcinoma With the Intrahepatic Arterial Injection of an Emulsion of Lipiodol and Idarubicin (Zavedos®): Phase I Study

NCT02028949 | Completed Phase 1

• 1 other identifier: GUIU APJ 2012
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Unresectable, non-metastatic cirrhosis-related hepatocellular carcinoma (HCC) has a poor prognosis as there are no recommended curative treatments. Chemoembolisation is the most widely used treatment in these patients, but this technique can prove to be toxic. intrahepatic arterial chemotherapy with lipiodol and idarubicin could be an effective therapeutic approach, without deteriorating liver function. The rationale for this treatment can be resumed as follows:

• HCC are vascularised via the hepatic artery system
• The IHA perfusion of anthracyclines leads to high elimination via the liver with low systemic concentrations
• The absence of embolisation reduces toxicity
• the toxiciity profile of idarubicin is well known and the drug is widely used for the IV treatment of leukemia
• idarubicin is the most cytotoxic drug for tumor cell lines.
• The in vitro cytotoxicity of idarubicin is 100% at low concentrations
• Lipiodol can stay in contact with tumor tissue for several weeks after injection and act as a vector for the drug
• The idarubicin-lipiodol is more stable than lipidol emulsions usually given by intraarterial injection
• The emulsion is more stable with idarubicin than with other anticancer molecules
• Sequential inclusion in accordance with the "continual reassessment method" makes it possible to increase inclusions at a target toxicity level while reducing inclusions at doses that are too low or too toxic The aim of the treatment is to improve survival.

Conditions

Child A/B7 Cirrhosis; Unresectable Non-metastatic Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• tolerance: toxicity will be evaluated according to the NCI CTC AE version 4.03 scale to determine the limiting dose

  7 weeks after the 2 injections

Secondary Outcomes (5)

• Study the pharmacokinetics of idarubicin in this delivery method

  24 months

• Evaluate overall survival

  24 months

• Evaluate progression-free survival

  24 months

• Evaluate time to progression

  24 months

• Evaluate the rate of objective response

  24 months

Study Arms (1)

Chemo-lipiodol

EXPERIMENTAL

Drug: Zavedos®; Other: Blood samples

Interventions

Zavedos® DRUG

Chemo-lipiodol

Blood samples OTHER

Chemo-lipiodol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-proven hepatocellular carcinoma or carcinoma meeting validated non-invasive criteria (EASL, AASLD)
• Child-Pugh A OR B7 cirrhosis
• General health status WHO 0.1
• Platelets \> 50 000/mm3, Polynuclear neutrophils \> 1000/mm3
• Creatininemia \< 1.5 times upper limit of normal
• LVEF by MUGA scan or US \> 50 %
• Age \> 18 years
• Signed informed consent
• For women child-bearing age, an effective means of contraception

You may not qualify if:

• Patients who can benefit from curative treatment (surgical resection, liver transplant or treatment via percutaneous destruction)
• Non-cirrhotic liver
• Cirrhosis Child B8 or B9 or C
• Extrahepatic metastases (pulmonary micronodules \< 7mm are not considered a contra-indication)
• Digestive hemorrhage within the previous month
• Patient on anticoagulants
• Pregnant women
• Uncontrolled infection
• Hypersensitivity to anthracyclines
• Hypersensitivity to iodine contrast agents
• Patient under guardianship or ward of court
• Patients who have already received the recommended cumulative dose of anthracycline (93 mg/m2 for idarubicin, 140 mg/m2 for mitoxantrone, 550 mg/m2 for doxorubicin, 600 mg/m2 for daunorubicin, 900 mg/m2 for epirubicin)

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead

Study Sites (1)

CHU de Dijon

Dijon, 21079 Cedex, France

Location

Related Publications (1)

• 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.

  PMID: 29427728 RESULT

MeSH Terms

Interventions

Idarubicin; Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2013
• First Posted: January 7, 2014
• Study Start: November 22, 2012
• Primary Completion: November 1, 2015
• Study Completion: February 5, 2016
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

FR (1)