Chemoembolisation of Non Resectable, Non Metastatic Hepatocellular Carcinomas

Chemoembolisation of Non Resectable, Non Metastatic Hepatocellular Carcinomas Combining DC Bead Microspheres Loaded With Idarubicin (Zavedos®): Phase I Trial

The purpose of this study is to determine the maximal tolerated dose of idarubicin for chemoembolization of non resectable non metastatic hepatocellular carcinoma.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Drug: idarubicin

Detailed Description

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third most common cause of cancer-related death worldwide. Most of the patients are diagnosed at intermediate-advanced stage when the sole standard treatment is transarterial chemoembolization (TACE). In the literature, survival rates in TACE studies vary widely and finally, there is no suggestion for the best chemotherapeutic agent or the optimal treatment regimen.

We hypothesise that the use of idarubicin (the most cytotoxic drug on HCC cell lines) in DC Bead would enhance the efficacy of TACE. The primary objective of the study is to determine the maximal tolerated dose of idarubicin in DC Bead for chemoembolization of non resectable non metastatic hepatocellular carcinoma.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Burgundy
    • Dijon, Burgundy, France, 21000
      • Centre Hospitalier Universitaire de Dijon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hepatocellular carcinoma cytologically or histologically proved or diagnosed according the criteria of the American Association for the Study of Liver Diseases(AASLD 2005)
• Three nodules maximum (unilobar disease without limitation in the number of nodules; 3 maximum nodules if bilobar disease [satellite nodules <1cm not included in the total sum])
• Child-Pugh score A or B7
• ECOG Performance Status < 2
• Platelet count > 50,000/µl and absolute neutrophil count (ANC) >1,000/µl
• Serum creatinine < 150 µmol/l
• Resting ejection fraction > 50% (echocardiography or isotopic method)
• Age > 18 years
• Signed written informed consent

Exclusion Criteria:

• Patients eligible for surgical resection or hepatic transplantation or radiofrequency ablation
• Extrahepatic metastases
• Known gastrointestinal bleeding up to 30 days before study entry
• Patients with anticoagulant treatment
• Evidence of portal vein thrombosis
• Pregnancy
• Clinically serious infection
• Known hypersensitivity to anthracyclines
• Known hypersensitivity to contrast medium

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Idarubicin; Dose escalation: level0 = idarubicin 5mg, level1 = idarubicin 10mg, level2 = idarubicin 15mg, level3 = idarubicin 20mg, level4 = idarubicin 25mg	Drug: idarubicin; Transarterial chemoembolization (in the hepatic artery) with idarubicin 5mg or 10 mg or 15 mg or 20 mg or 25 mg injected in a solution of 2ml DC Bead (300 µm-500µm); 1 unique course; Other Names: IDA; 4-MDR; IMI 30

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose-limiting toxicity assessed according NCI CTC AE v3.0	Within the first month after chemoembolization

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective responses according criteria of the European Association for the Study of the Liver and according RECIST criteria.	2 months
Quality of life (EORTC QLQ-C30)	2 months
Pharmacokinetics parameters of idarubicin and idarubicinol	Within 72 hours after chemioembolization

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Dijon
• Investigators: Principal Investigator: Laurent BEDENNE, MD Ph.D, Centre Hospitalier Universitaire Dijon

Publications and helpful links

General Publications

• Anota A, Boulin M, Dabakuyo-Yonli S, Hillon P, Cercueil JP, Minello A, Jouve JL, Paoletti X, Bedenne L, Guiu B, Bonnetain F. An explorative study to assess the association between health-related quality of life and the recommended phase II dose in a phase I trial: idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma. BMJ Open. 2016 Jun 24;6(6):e010696. doi: 10.1136/bmjopen-2015-010696.
• Boulin M, Hillon P, Cercueil JP, Bonnetain F, Dabakuyo S, Minello A, Jouve JL, Lepage C, Bardou M, Wendremaire M, Guerard P, Denys A, Grandvuillemin A, Chauffert B, Bedenne L, Guiu B. Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma: results of the IDASPHERE phase I trial. Aliment Pharmacol Ther. 2014 Jun;39(11):1301-13. doi: 10.1111/apt.12746. Epub 2014 Apr 16.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: December 28, 2009
• First Submitted That Met QC Criteria: December 28, 2009
• First Posted (Estimate): December 29, 2009

Study Record Updates

• Last Update Posted (Estimate): January 9, 2013
• Last Update Submitted That Met QC Criteria: January 8, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Idarubicin
• Other Study ID Numbers: IDASPHERE