Phase 1 Study of Hepatic Intra-Arterial Administration of 188RE-SSS Lipiodol to Treat HepatoCellular Carcinomas
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Center Eugene Marquis
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Maximal tolerated dose
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
Rhenium Lipiodol
Hepatic Intra-Arterial Administration of radio-active lipiodol.
Intervention: 188Re-SSS Lipiodol (Drug)
Outcomes
Primary Outcomes
Maximal tolerated dose
Time Frame: Injection each week during 4 weeks and at month 2
Toxicity CTC grade ≥ 3 with CTCAE version 4.
Secondary Outcomes
- Bio-availability(1, 6, 24 et 48 hours after treatment injection)