188re-sss lipiodol to treat hepatocellular carcinomas

Conditions: Hepatocellular Carcinomas

Summary: this study is to determine the maximum tolerated dose and the recommended 188re-sss lipiodol activity for hepatic intra-arterial injection in patients with hepato-cellular carcinoma. the new radioactive isotope 188rhenium associated with lipiodol is expected to reduce the radioprotection constraints and hence the duration of the hospitalisation in a protected room from 8 to 1 day.

hepatocellular carcinoma is one of the most prevalent primary cancers in many countries. in france, mortality due to hcc on viral c cirrhosis is going to increase of about 150% for men and 200% for women until 2020. consequently, hcc is a problem of public health. the current treatment for hcc is mainly palliative with chemoembolization or intra-arterial radiotherapy, and intra-arterial targeted radiotherapy being the best tolerated method (iodine-131-labelled lipiodol being the most commonly used). however, since 2007, a new therapeutic approach can be considered with oral sorafenib, an anti-angiogenic drug which increases slightly the survival of patients. the key for an efficient treatment of hcc is presumably a co-treatment of sorafenib and intra-arterial radiotherapy. the 131i-lipiodol is a good candidate but presents disadvantages: it requires hospitalization in a radionuclide therapy room for one week. therefore, it is necessary to find new radioactive labellings for lipiodol. in this objective, 188re-sss lipiodol, a new radioactive labeled stable complex has been developed. it has a short half-life and a tiny amount of gamma radiation compared to 131i-lipiodol, so it allows to reduce hospitalization in a protected room from 8 days to only one day. the aim of this study is to determine the maximum tolerated dose and thus the recommended activity of 188re-sss lipiodol by intra-arterial injection in patients with hcc.

Eligibility criteria:
inclusion criteria: * adult over 18, * who performance status ≤ 2, * hepatocellular carcinoma histologically or cytologically proven, or association of liver tumor with chronic hepatopathy and afp \> 400 ng/ml, or tumorous hepatic formation considered as hypervascularised by at least 2 methods of imaging in cirrhotic patient, non operable, non resectable, non transplantable, non accessible to percutaneous treatment tumor, * measurable tumor, uni- or multinodular, taking up less than 50% of hepatic volume, * stage a to c of the bclc classification (or stage 0 to 4 of the clip) with: * no thrombosis of the portal vein, therapeutic escape or intolerance causing the end of the treatment or contraindication to sorafenib * if thrombosis of the portal vein, therapeutic escape to lipiocis, * possibility of treatment by intra-arterial radiotherapy over a decision of a multidisciplinary committee, * written informed consent exclusion criteria: * patient with a stage ≥ 3 toxicity of the ctcae version 4 * stage d of the classification bclc * acute impairment of hepatic functions (child-pugh b9 or c) * grade iii hepatocarcinoma of the okuda classification * encephalopathy with troubles even moderated of cognitive functions * advanced chronic respiratory insufficiency * creatinine clearance \ 2,3) * contraindication to the intra-arterial administration * patients who can't be followed up for psychological or geographic reasons * patients dependant on another person for daily care * urinary incontinence * progressive cancer * pregnant or breastfeeding woman, or not using adequate effective contraception method

Keywords: hepatocellular carcinomas lipiodol rhenium non operable hepatocellular carcinomas