Clinical trial NCT01040559: Chemoembolisation of Non Resectable, Non Metastatic Hepatocellular Carcinomas
Official title: Chemoembolisation of Non Resectable, Non Metastatic Hepatocellular Carcinomas Combining DC Bead Microspheres Loaded With Idarubicin (Zavedos®): Phase I Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Centre Hospitalier Universitaire Dijon
Sponsor class: OTHER
First posted: 2009-12-29
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Dose-limiting toxicity assessed according NCI CTC AE v3.0
timeFrame: Within the first month after chemoembolization
Secondary outcomes:
measure: Objective responses according criteria of the European Association for the Study of the Liver and according RECIST criteria.
timeFrame: 2 months
measure: Quality of life (EORTC QLQ-C30)
timeFrame: 2 months
measure: Pharmacokinetics parameters of idarubicin and idarubicinol
timeFrame: Within 72 hours after chemioembolization
Other outcomes:
Locations:
city: Dijon
country: France
facility: Centre Hospitalier Universitaire de DIJON
state: Burgundy
Study officials:
affiliation: Centre Hospitalier Universitaire Dijon
name: Laurent BEDENNE, MD Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.