Clinical Trials Register

Summary
EudraCT Number:	2018-002163-26
Sponsor's Protocol Code Number:	PRI2017HUS7040
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-06-04
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2018-002163-26

A.3

Full title of the trial

Pilot study on doxorubicin kinetic distribution during arterial chemoembolization

Etude pilote de la cinétique de distribution de la Doxorubicine lors de la chimio-embolisation artérielle

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Pilot study on doxorubicin kinetic distribution during arterial chemoembolization

Etude pilote de la cinétique de distribution de la Doxorubicine lors de la chimio-embolisation artérielle

A.3.2

Name or abbreviated title of the trial where available

CINEDOXO

A.4.1

Sponsor's protocol code number

PRI2017HUS7040

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Hôpitaux Universitaires de Strasbourg
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Hôpitaux Universitaires de Strasbourg
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hôpitaux Universitaires de Strasbourg
B.5.2	Functional name of contact point	Direction de la Recherche Clinique
B.5.3	Address:
B.5.3.1	Street Address	1, place de L'hôpital
B.5.3.2	Town/ city	Strasbourg
B.5.3.3	Post code	67091
B.5.3.4	Country	France
B.5.4	Telephone number	330388115415
B.5.5	Fax number	330388116799
B.5.6	E-mail	drci@chru-strasbourg.fr

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	ADRIBLASTINE 50mg, poudre solution injectable en flacon
D.2.1.1.2	Name of the Marketing Authorisation holder	PFIZER HOLDING FRANCE
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intraarterial use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FLUORESCEIN SODIUM
D.3.9.3	Other descriptive name	FLUORESCEIN SODIUM
D.3.9.4	EV Substance Code	SUB13905MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intraarterial use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SODIUM CHLORIDE
D.3.9.3	Other descriptive name	SODIUM CHLORIDE 0.9%
D.3.9.4	EV Substance Code	SUB171043
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.9
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	VISIPAQUE (Iodixanol)
D.2.1.1.2	Name of the Marketing Authorisation holder	GE HEALTHCARE SAS
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intraarterial use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

hepatocellular carcinoma

E.1.1.1

Medical condition in easily understood language

liver cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10049010
E.1.2	Term	Carcinoma hepatocellular
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

intratumoral doxorubicin kinetic distribution assessment with histological analysis as part of lipiodol transarterial chemoembolization, depend on used reconstitution solvent (NaCL 0.9% VS Visipaque)

Evaluation de la cinétique de distribution intratumorale de la Doxorubicine par analyse histologique dans le cadre du traitement CET lipiodolée, selon le solvant de reconstitution utilisé (sérum physiologique ou agent de contraste iodé non-ionique iso-osmolaire).

E.2.2

Secondary objectives of the trial

1. Assessment of solvent influence used to Doxorubicine dissolution on intratumoral doxorubicin distribution kinetic with Confocal Lazer Endomicroscopy (CLE)

2. Safety evaluation

1. Evaluation de l’influence du solvant utilisé pour la dissolution de la doxorubicine sur la cinétique de distribution intratumorale de la Doxorubicine par endomicroscopie confocale laser.
2. Evaluation de la sécurité

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- man and womanof 18 years old or older
- Subject affiliated to social security
- Subject able to understand study scope and rick and give signed informed consent
- histological, cytological or radiological confirmed diagnosis of Hepatocellular carcinoma:
 stade A (patient with transplant pending) and Class B according to BCLC Classification
 Sated A and Baccording to Child-Pugh classification
- chemoembolization indicated for unresecable hepatocellular carcinoma
- biological parmaters allowing chemoembolization procedure (platelet count, bilirubin, INR ≤ 1,5, SGPT/SGOT<5N, albumin>2,5g/dl)
- ECOG performance status ≤ 2
- effective contracpetion during all study
- negative prenancy test for woman child-bearing

- Patient majeur homme ou femme
- Patient ayant signé un consentement éclairé
- Patient pour lequel le diagnostic confirmé par histologie, cytologie, ou radiologie de CHC de stade :
 stade A pour les patients en attente d’une transplantation et de classe B selon la classification BCLC
 stades A et B selon la classification Child-Pugh
- Patient ayant une indication de chimio-embolisation d’un carcinome hépatique non résécable
- Patient ayant des paramètres biologiques (numération plaquettaire, bilirubine, INR ≤ 1,5, ASAT/ALAT<5N, albumine>2,5g/dl) lui permettant de bénéficier d’une chimio-embolisation
- Patient ayant un statut de performance ECOG ≤ 2 à l’inclusion
- Sujet affilié à un régime de protection sociale d’assurance maladie
- Sujet apte à comprendre les objectifs et les risques liés à la recherche et à donner un consentement éclairé daté et signé
- Pour une femme en âge de procréer : test de grossesse sanguin négatif
- Les hommes et femmes en âge de procréer doivent accepter de suivre une contraception hautement efficace jusqu’à la fin de l’étude. La contraception hautement efficace est défini par :

E.4

Principal exclusion criteria

- Any contra-indication for the procedure of transarterial Chemoembolization, angiography, endomicroscopie, and hepatic biopsy ponction
- blood coagulation parameters abnormalities (TP < 50% and/or platelet <50000 /mm3 and/or ratio TCA <1,5) in spite of hemostatic measure correction
- Any contra-indication for fluorescein, Adriblastin®, Lipiodol®, Visipaque® , Gelita spon®, Avitène
- hyperthyroidism proved undiagnosed
- ilirubine totale > 40 µmol/L
- Créatinin > 2mg/dl
- GFR < 30ml/min/m2
- Neutrophiles < 1500/mm3 ou Plaquettes < 50000/µl
- Hémoglobin < 9g/dl
- white cells < 2500/mm3
- full or flux invesion of portal vein thrombosis
- extrahepatic metastasis
- transplant list inscription
- exophytic or sub capsilaire tumor, with no percutaneous access accross healthy liver with coaxial needle
- exclusion period
- subject unable to understand study information
- Psychiatric disorders and adults under guardianship
- Pregnancy or breastfeeding
- Patients under judicial protection

- Contre-indication à la réalisation de la CET, de l’angiographie, de l’endomicroscopie, de la ponction de biopsie hépatique
- Trouble de la coagulation sanguine malgré les mesures de correction de la crase sanguine, caractérisés par TP < 50% et/ou plaquettes<50000 /mm3 et/ou ratio TCA <1,5).
- Contre-indication à l’utilisation de fluorescéine, Adriblastine®, Lipiodol®, Visipaque® , Gelita spon®, Avitène
- Hyperthyroïdie avérée non bilantée
- Bilirubine totale > 40 µmol/L
- Créatinine > 2mg/dl
- Débit de Filtration Glomérulaire < 30ml/min/m2
- Neutrophiles < 1500/mm3 ou Plaquettes < 50000/µl
- Hémoglobine < 9g/dl
- Globules blancs < 2500/mm3
- Thrombose veineuse porte complète ou inversion du flux
- Métastases extra-hépatiques
- Patient inscrit sur liste de greffe
- Tumeur sous-capsulaire ou exophytique, ne permettant pas l’accès percutané à travers le foie sain pour l’aiguille coaxiale
- Patient en période d’exclusion (déterminée par une étude précédente ou en cours)
- Patient incapable de recevoir ou comprendre les informations relatives à l’étude
- Patient sous sauvegarde de justice
- Patient sous tutelle ou curatelle
- Grossesse
- Allaitement

E.5 End points

E.5.1

Primary end point(s)

Histological analysis :
- distribution, frequence, fluorescence intensity frome tumor and adjacent non tumoral hepatic tissu
- tissular slide doxorubicin quantification : flourescence produce by tissular compartment and surface

E.5.1.1

Timepoint(s) of evaluation of this end point

at the end of study

E.5.2

Secondary end point(s)

n° 1 : Confocal lazer endomicroscopie :
- time of emulsion arrival
- time of drug delivery
- time of droplet fusion

n° 2 : collection of study adverse event and serious adverse event

E.5.2.1

Timepoint(s) of evaluation of this end point

n° 1 : during chemoembolization procédure

n°2 : during all the study

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

au terme de la dernière visite du dernier patient suivi dans la recherche

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

none

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-07-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-06-26

P. End of Trial
P.	End of Trial Status	Completed

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