Trial Information

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

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.