Hepatocellular Carcinomas
Conditions
Keywords
Hepatocellular carcinomas, lipiodol, rhenium, Non operable Hepatocellular carcinomas
Brief 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.
Detailed description
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.
Interventions
Hepatic Intra-Arterial Administration of radio-active lipiodol.
Sponsors
Rennes University Hospital
Center Eugene Marquis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 \< 55 ml/min, polynuclear neutrophils \< 1500 G/L, platelets \< 50 G/L, prothrombin \< 40% (INR \> 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal tolerated dose | Injection each week during 4 weeks and at month 2 | Toxicity CTC grade ≥ 3 with CTCAE version 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bio-availability | 1, 6, 24 et 48 hours after treatment injection | Measurement by gamma-scintigraphy and by measurement of radio-activity in urinary, faecal and blood samples. |
Countries
France
Outcome results
None listed