Kinectics of Distribution of Doxorubicin-Lipiodol Emulsion in c-TACE (CineDoxo)

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

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.

Study Overview

• Status: Completed
• Conditions: Hepato Cellular Carcinoma
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Strasbourg, France, 67000
    • University Hospital, Strasbourg, France

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Iodinate contrast; 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; Super selective transarterial chemoembolization of CHC, with doxorubicin reconstituted in 5cc iso-osmolar ionic iodinated contrast media
ACTIVE_COMPARATOR: Normal saline; Doxorubicin solution reconstituted in 5 mL normal saline	Drug: Super selective transarterial chemoembolization of CHC, with doxorubicin reconstituted in 5cc normal saline; Super selective transarterial chemoembolization of CHC, with doxorubicin reconstituted in 5cc normal saline

What is the study measuring?

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,

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France
• Investigators: Principal Investigator: Iuian 03 69 55 15 27, MD, University Hospital, Strasbourg, France

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 26, 2018
• Primary Completion (ACTUAL): October 9, 2019
• Study Completion (ACTUAL): October 9, 2019

Study Registration Dates

• First Submitted: October 2, 2018
• First Submitted That Met QC Criteria: October 12, 2018
• First Posted (ACTUAL): October 15, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 27, 2020
• Last Update Submitted That Met QC Criteria: July 24, 2020
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Doxorubicin; Conventional transarterial chemoembolization (c-TACE); Kinetics of distribution
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: 7040

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No