188RE-SSS Lipiodol to Treat HepatoCellular Carcinomas (LIP-RE-I)

Center Eugene Marquis

Status and phase

Completed

Phase 1

Conditions

Hepatocellular Carcinomas

Treatments

Drug: 188Re-SSS Lipiodol

Study type

Interventional

Funder types

Other

Identifiers

NCT01126463

LIP-RE-I

Details and patient eligibility

About

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.

Full 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.

Enrollment

16 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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