188RE-SSS Lipiodol to Treat HepatoCellular Carcinomas

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 1 Study of Hepatic Intra-Arterial Administration of 188RE-SSS Lipiodol to Treat HepatoCellular Carcinomas

Conditions
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Hepatocellular Carcinomas

Intervention / Treatment
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* Drug: 188Re-SSS Lipiodol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rhenium Lipiodol<br>Hepatic Intra-Arterial Administration of radio-active lipiodol. | Drug: 188Re-SSS Lipiodol<br>* Hepatic Intra-Arterial Administration of radio-active lipiodol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal tolerated dose | Toxicity CTC grade ≥ 3 with CTCAE version 4. | Injection each week during 4 weeks and at month 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bio-availability | Measurement by gamma-scintigraphy and by measurement of radio-activity in urinary, faecal and blood samples. | 1, 6, 24 et 48 hours after treatment injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular carcinomas, lipiodol, rhenium, Non operable Hepatocellular carcinomas