Trial for Hepatocellular Carcinoma Adjuvant Treatment by Lipiocis

Sponsor

ANRS, Emerging Infectious Diseases (Other)

Overall Status

Completed

CT.gov ID

NCT00116454

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The recurrence of hepatocellular carcinoma (HCC), two years after curative treatment is high, about 40% - 50%. Recently, it has been shown that intra-arterial radioactive lipiodol (Lipiocis®) could reduce the recurrence of cancer and increase the survival after resection of HCC developed on cirrhosis B. The aim of the present trial is to investigate the effect of Lipiocis® in preventing recurrence after curative treatment of HCC in patients with viral or alcoholic hepatitis related cirrhosis by surgical or percutaneous ablation.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Hepatocellular Hepatitis, Viral, Human	Drug: 131 I-lipiodol	Phase 3

Detailed Description

The usual therapeutic approaches of early hepatocellular carcinoma (HCC) are partial hepatectomy or percutaneous ethanol injection. However, these therapeutic procedures do not suppress the cirrhotic liver tissue which represents a major risk factor for recurrence and/or occurrence of a second tumor in the liver. Recently, it has been shown that intra-arterial radioactive lipiodol (Lipiocis®) could reduce the recurrence of cancer and increase the survival after resection of HCC developed on cirrhosis B. The aim of the present randomized and multicenter trial is to investigate the effect of iodine-131-labelled lipiodol (131I-lipiodol = Lipiocis®) in preventing recurrence after curative treatment of HCC (hepatocellular carcinoma) in patients with viral or alcoholic hepatitis related cirrhosis by surgical or percutaneous ablation. The period of this study will be 3 years including 1 year for the enrollment and 2 years for the follow-up. Fifty patients will receive one 2200 MBq dose of Lipiocis and 50 patients will not be treated by Lipiocis (control group). The intra-arterial hepatic administration of Lipiocis will occur 11 to 12 weeks after the initial curative treatment.

The inclusion criteria are as follows : 1) men or women, aged between 18 and 75 years old, with cirrhosis or chronic hepatitis associated with C, B, delta infection or alcool intake or both and confirmed by liver biopsy and 2) one or two HCC nodules treated by surgical or percutaneous ablation (ethanol, acetic acid 50% or radiofrequency).

The efficacy of the initial curative treatment will be assessed by the following criteria:

alpha-fetoprotein concentration below 25ng/ml, no progression in size of the tumour demonstrated by ultrasonography and no arterial hypervascularization on CT scan imaging.

The patients with the following criteria will be excluded: co-infection with HIV (Human Immunodeficiency Virus)associated with a CD count <200/mm3 and a viral charge >5000 HIV RNA copies/ml, documented iodine intolerance, respiratory disease, decompensated cirrhosis (Child-Pugh score over or equal 8), bilirubin concentration over 51µmol/l, portal or hepatic vein thrombosis, extra-hepatic metastasis, excessive alcohol intake (over 50g per day), blood platelet count below 50,000/mm3, neutrophil count below 1500/mm3, creatininemia over 120µmol/l, other severe concurrent disease, previous treatment for hepatocellular carcinoma and women who can be pregnant or breastfeeding.

The main endpoint will be to determine whether the Lipiocis® treatment reduces the percentage of recurrence from 50% to 20% at 24 months. The secondary end-points will be the overall survival, the survival without recurrence of the primary tumor, the survival without new tumor, the deterioration of hepatocellular function and the side effects of the Lipiocis® treatment.

Study Design

Study Type:

Interventional

Actual Enrollment :

73 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized and Multicenter Trial for Hepatocellular Carcinoma Adjuvant Treatment by Lipiocis

Study Start Date :

Jul 1, 2005

Actual Primary Completion Date :

Aug 1, 2013

Actual Study Completion Date :

Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: lipiocis group intra-arterial hepatic administration, one 2200 MBQ dose, duration of treatment 1 week	Drug: 131 I-lipiodol intra-arterial hepatic administration of Lipiocis will occur, 11 to 12 weeks after the initial curative treatment Other Names: Lipiocis
No Intervention: control group group untreated

Arm

Intervention/Treatment

Experimental: lipiocis group

intra-arterial hepatic administration, one 2200 MBQ dose, duration of treatment 1 week

Drug: 131 I-lipiodol

intra-arterial hepatic administration of Lipiocis will occur, 11 to 12 weeks after the initial curative treatment

Other Names:

Lipiocis

No Intervention: control group

group untreated

Outcome Measures

Primary Outcome Measures

to determine if the Lipiocis treatment decreases the % of tumoral recurrence after 24 months, judged on the rise of alpha-fetoprotein and the reappearance of one or more tumours on the hepatic CT scan [at 24 Months]

Secondary Outcome Measures

overall survival [at 24 months]
recurrence-free survival [at 24 months]
treatment toxicity [at 24 months]
Deterioration of the hepatocellular function [at 24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men or women , aged between 18 and 75 years old
Cirrhosis or chronic hepatitis associated with C, B, delta infection or alcool intake or both and confirmed by liver biopsy
One or two HCC nodules treated by surgical or percutaneous ablation (ethanol, acetic acid 50% or radiofrequency).
The efficacy of the initial curative treatment will be assessed by the following criteria: alpha-fetoprotein concentration < or equal 25ng/ml, no progression in size of the tumour demonstrated by ultrasonography and no arterial hypervascularization on CT scan imaging

Exclusion Criteria:

HIV coinfection associated with a CD count<200/mm3 and a viral charge>5000 HIV RNA copies/ml
Documented iodine intolerance
Respiratory insufficiency
Decompensated cirrhosis (Child-Pugh score over 8)
Bilirubin concentration over 51 µmol/l
Portal or hepatic vein thrombosis
Extra-hepatic metastasis
Excessive alcohol intake (over 50g per day)
Blood platelet count below 50000/mm3
Neutrophil count above 1500/mm3
Creatininemia over 120µmol/l
Myocardial infarction or rhythm disorders
Psychiatric disease with hospitalization
Previous treatment for hepatocellular carcinoma
Pregnant or breastfeeding
Treatment with interferon and/or ribavirin 3 months before inclusion
Treatment with tamoxifen or somatostatin analogs or systemic chemotherapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Service d'Hépatologie Hôpital Saint Antoine	Paris		France	75012

Sponsors and Collaborators

ANRS, Emerging Infectious Diseases

Investigators

Principal Investigator: Olivier Rosmorduc, MD, Hopital Saint Antoine SERVICE D'HEPATOLOGIE
Study Director: Fabrice Carrat, MD, INSERM U 444 FACULTE DE MEDECINE ST ANTOINE