188RE-SSS Lipiodol to Treat HepatoCellular Carcinomas

Hepatocellular Carcinomas Clinical Trial

— LIP-RE-I  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01126463
• Other study ID #: LIP-RE-I
• Status: Completed
• Phase: Phase 1
• Start date: May 26, 2010
• Est. completion date: August 6, 2019

Study information

• Verified date: July 2020
• Source: Center Eugene Marquis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: August 6, 2019
• Est. primary completion date: August 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinomas

Intervention

Drug:
• 188Re-SSS Lipiodol
Hepatic Intra-Arterial Administration of radio-active lipiodol.

Locations

Country	Name	City	State
France	Centre Eugene Marquis	Rennes

Sponsors (2)

Lead Sponsor	Collaborator
Center Eugene Marquis	Rennes University Hospital

Country where clinical trial is conducted

France, 

References & Publications (1)

Garin E, Rakotonirina H, Lejeune F, Denizot B, Roux J, Noiret N, Mesbah H, Herry JY, Bourguet P, Lejeune JJ. Effect of a 188 Re-SSS lipiodol/131I-lipiodol mixture, 188 Re-SSS lipiodol alone or 131I-lipiodol alone on the survival of rats with hepatocellular carcinoma. Nucl Med Commun. 2006 Apr;27(4):363-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal tolerated dose	Toxicity CTC grade = 3 with CTCAE version 4.	Injection each week during 4 weeks and at month 2
Secondary	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