Chemoembolisation of Non Resectable, Non Metastatic Hepatocellular Carcinomas

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

Detailed Description
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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.

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

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: idarubicin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Idarubicin<br>Dose escalation: level0 = idarubicin 5mg, level1 = idarubicin 10mg, level2 = idarubicin 15mg, level3 = idarubicin 20mg, level4 = idarubicin 25mg | Drug: idarubicin<br>* 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<br>* Other names: IDA;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |