Kinectics of Distribution of Doxorubicin-Lipiodol Emulsion in c-TACE

Study Overview
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Brief Summary
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Conventional transarterial chemoembolization with Doxorubicin (c-TACE) is the gold standard treatment for Hepato Cellular Carcinoma (HCC) stage B (BCLC) / stages A and B (Child-Pugh). Clinical recommendations for cTACE indicate that the doxorubicin solution may be reconstituted in either aqueous solution or iso-osmolar ionic iodinated contrast media. There is no consensus on which solvent should be used. Hence, the clinical evaluation of Lipiodol cTACE would benefit from a standardization in the reconstitution of the drug. In this study, the comparison of the kinetics of distribution of the drug within the tumor micro-environment is expected to allow for comparison of drug solvents. This pilot study aims at evaluating the kinetics of distribution of the drug within the tumor micro-environment, for the two main solvents used in reconstituting the drug, namely normal saline and contrast media. The kinetics of distribution in the tumor will be evaluated primarily through regular biopsy sampling, and secondary with confocal laser endomicroscopy.

Official Title
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Kinectics of Distribution of Doxorubicin-Lipiodol Emulsion in c-TACE: a Pilot Study

Conditions
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Hepato Cellular Carcinoma

Intervention / Treatment
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* Drug: Super selective transarterial chemoembolization of CHC, with doxorubicin reconstituted in 5cc iso-osmolar ionic iodinated contrast media
* Drug: Super selective transarterial chemoembolization of CHC, with doxorubicin reconstituted in 5cc normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (>18) Informed consent CHC Child-Pugh stage A or B, BCLC stage B Referred for chemoembolization of a non-surgery-candidate CHC Blood test results compatible with cTACE (INR ≤ 1,5, ASAT/ALAT<5N, albumine>2,5g/dl) Exclusion Criteria: Contraindication to cTACE, angiography, confocal laser endomicroscopy or liver biopsy Hyperthyroidism Contraindication to the use of fluorescein, Ariblastine,Lipiodol, Visipaque, Gelita spon, Avitene extra hepatic metastasis Subcapsular or exophytic tumor impeding direct percutaneous access through healthy liver tissue Waiting list for liver transplant Complete portal venous thrombosis or flow inversion Pregnancy or breast feeding Protected major (Guardianship) Patient in situation of exclusion (determined by a previous or ongoing study) Subject incapacity to understand informed consent

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Iodinate contrast<br>Doxorubicin solution reconstituted in 5 mL iso-osmolar ionic iodinated contrast media | Drug: Super selective transarterial chemoembolization of CHC, with doxorubicin reconstituted in 5cc iso-osmolar ionic iodinated contrast media<br>* Super selective transarterial chemoembolization of CHC, with doxorubicin reconstituted in 5cc iso-osmolar ionic iodinated contrast media<br>|
| Active Comparator: Normal saline<br>Doxorubicin solution reconstituted in 5 mL normal saline | Drug: Super selective transarterial chemoembolization of CHC, with doxorubicin reconstituted in 5cc normal saline<br>* Super selective transarterial chemoembolization of CHC, with doxorubicin reconstituted in 5cc normal saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological analysis of biopsy samples for the evaluation of the kinetics of distribution of doxorubicine in tumor compartments depending on the solvent used for drug reconstitution | Biopsy samples of liver tumor tissue. Histological analysis will provide a quantification of the doxorubicin drug in tumor compartment. | T0: 1 min before cTACE drug injection star | 
| Histological analysis of biopsy samples for the evaluation of the kinetics of distribution of doxorubicine in tumor compartments depending on the solvent used for drug reconstitution | Biopsy samples of liver tumor tissue. Histological analysis will provide a quantification of the doxorubicin drug in tumor compartment. | T1 : 2 min after cTACE drug injection started | 
| Histological analysis of biopsy samples for the evaluation of the kinetics of distribution of doxorubicine in tumor compartments depending on the solvent used for drug reconstitution | Biopsy samples of liver tumor tissue. Histological analysis will provide a quantification of the doxorubicin drug in tumor compartment. | T2: 1 second after half of cTACE drug has been injected | 
| Histological analysis of biopsy samples for the evaluation of the kinetics of distribution of doxorubicine in tumor compartments depending on the solvent used for drug reconstitution | Biopsy samples of liver tumor tissue. Histological analysis will provide a quantification of the doxorubicin drug in tumor compartment. | T3: 1 min after cTACE drug injection is completed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In vivo evaluation of the kinetics of distribution of doxorubicine in tumoral tissue with confocal laser endomicroscopy, depending on the solvent used for drug reconstitution | Continuous image recording (videos) through the course of the cTACE drug injection, from 1 minute before drug injection starts to the time when cTACE drug injection is completed | 1 min before cTACE drug injection starts, | 
| In vivo evaluation of the kinetics of distribution of doxorubicine in tumoral tissue with confocal laser endomicroscopy, depending on the solvent used for drug reconstitution | Continuous image recording (videos) through the course of the cTACE drug injection, from 1 minute before drug injection starts to the time when cTACE drug injection is completed | 2 min after cTACE drug injection started, | 
| In vivo evaluation of the kinetics of distribution of doxorubicine in tumoral tissue with confocal laser endomicroscopy, depending on the solvent used for drug reconstitution | Continuous image recording (videos) through the course of the cTACE drug injection, from 1 minute before drug injection starts to the time when cTACE drug injection is completed | 1 second after half of cTACE drug has been injected, | 
| In vivo evaluation of the kinetics of distribution of doxorubicine in tumoral tissue with confocal laser endomicroscopy, depending on the solvent used for drug reconstitution | Continuous image recording (videos) through the course of the cTACE drug injection, from 1 minute before drug injection starts to the time when cTACE drug injection is completed | 1 min after cTACE drug injection is completed, | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Conventional transarterial chemoembolization (c-TACE), Doxorubicin, Kinetics of distribution