Clinical Trials Register

Summary
EudraCT Number:	2019-001920-36
Sponsor's Protocol Code Number:	NIMAO/2018-01/JF-01
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-09-18
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

2019-001920-36

A.3

Full title of the trial

Phase II a study to evaluate the safety, tolerability, distribution and dose effect of neoadjuvant doxorubicin arterial embolization in patients with prostate cancer at high risk of recurrence before radical prostatectomy

Etude de phase II a d’évaluation de la sécurité, de la tolérabilité, de la distribution et de l’effet dose d’une chimio embolisation artérielle néoadjuvante à la doxorubicine chez les patients porteurs d’un cancer de la prostate à haut risque de récidive avant prostatectomie radicale

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

CAPEMCHAR

A.4.1

Sponsor's protocol code number

NIMAO/2018-01/JF-01

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	CHU de NIMES
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	CHU de NIMES
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	CHU de NIMES
B.5.2	Functional name of contact point	DRCI
B.5.3	Address:
B.5.3.1	Street Address	Place du Pr Debré 30029 NIMES
B.5.3.2	Town/ city	Place du Pr Debré 30029 NIMES
B.5.3.3	Post code	30029
B.5.3.4	Country	France
B.5.4	Telephone number	+3300466684264
B.5.5	Fax number	+3300466683400
B.5.6	E-mail	drc@chu-nimes.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 50 mg, poudre pour 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.3.1	Product name	Chlorhydrate de Doxorubicine 50mg
D.3.4	Pharmaceutical form	Powder for concentrate for solution for injection/infusion
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

patients with high-risk prostate cancer with a Gleason score of 9-10 on biopsy,multimodal treatment radical prostatectomy validated in CPR, managed in Hospital of Nîmes.

patients porteurs d’un cancer de la prostate à haut risque avec un score de Gleason à 9-10 à la biopsie, traitement multimodal avec prostatectomie radicale validé en RCP, pris en charge au CHU de Nîmes.

E.1.1.1

Medical condition in easily understood language

patients with high-risk prostate cancer with a Gleason score of 9-10 on biopsy,multimodal treatment radical prostatectomy validated in CPR, managed in Hospital of Nîmes.

patients porteurs d’un cancer de la prostateavec un score de Gleason à 9-10 à la biopsie, traitement multimodal avec prostatectomie radicale validé en RCP, pris en charge au CHU de Nîmes.

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	10007113
E.1.2	Term	Cancer of prostate
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

evaluate the tolerance to prostatic embolization with doxorubicin-loaded beads according to the dose of chemotherapy used

évaluer la tolérance à la réalisation d’une embolisation prostatique aux billes chargées à la doxorubicine en fonction de la dose de chimiothérapie utilisée.

E.2.2

Secondary objectives of the trial

describe the distribution of beads, evaluate post-embolization and post-operative complications, the evolution at 1 and 3 months after surgery of the biological response (PSA assay), functional consequences (symptoms, incontinence, erectile dysfunction, quality of life).

décrire la distribution des billes, d’évaluer les complications post-embolisation et postopératoires, l’évolution à 1 et 3 mois après la chirurgie de la réponse biologique (dosage de la PSA), des conséquences fonctionnelles (symptômes, incontinence, dysfonction érectile, qualité de vie).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

General inclusion criteria :
- The patient must have given free and informed consent and signed it.
- The patient must be affiliated or beneficiary of a health insurance scheme.
- The patient is at least 18 years old (≥) and under 80 years old (<).
Inclusion criteria for the target population:
- Patient with high-risk prostate cancer with a Gleason score of 9-10 on biopsy, candidate for multimodal treatment with radical prostatectomy validated in CPR.

Critères d’inclusion généraux :
• Le patient doit avoir donné son consentement libre et éclairé et signé le consentement.
• Le patient doit être affilié ou bénéficiaire d’un régime d’assurance maladie.
• Le patient est âgé d’au moins 18 ans (≥) et de moins de 80 ans (<).
Critères d’inclusion concernant la population cible :
• Patient porteur d’un cancer de prostate à haut risque avec un score de Gleason à 9-10 à la biopsie, candidat à un traitement multimodal avec prostatectomie radicale validé en RCP.

E.4

Principal exclusion criteria

Exclusion criteria:
- The patient has penile collateral that does not allow embolization as a precautionary principle (effect on erection unknown).
- The control scintigraphy after Injection of the albumin macroaggregates labelled with TC 99 m in each artery shows a non-target fixation (rectum).
5.3 Criteria for non-inclusion of research subjects
General non-inclusion criteria :
- The patient is participating in another study.
- The patient is in an exclusion period determined by a previous study.
- The patient is under the protection of justice, guardianship or curatorship
- Patients who are unable to express their consent may not be asked for this research (e. g. persons undergoing psychiatric care whose mental disorders make consent impossible...)
- The patient refuses to sign the consent.
- It is impossible to give informed information about the subject.
Criteria for non-inclusion regarding interfering diseases or associated conditions:
- Patient with metastatic disease from the outset.
- Contraindication to surgery
- Contraindication for MRI (pacemaker not MRI compatible, claustrophobia, metal device, total hip replacement).
- Patient with a history of bifemoral aortobypass or other vascular surgery that condemns endovascular access to prostate arteries.
- Patient with non-reversible hemostasis disorder: TP < 50%, ACT > 2 times the control, Platelet < 60 G/L.

Critères d’exclusion :
• Le patient présente une collatérale pénienne ne permettant pas d’embolisation par principe de précaution (effet sur l’érection inconnu).
• La scintigraphie de contrôle après Injection des macro-agrégats d’albumine marqués au TC 99 m dans chaque artère montre une fixation non cible (rectum).
5.3 Critères de non-inclusion des personnes qui se prêtent à la recherche
Critères de non-inclusion généraux :
• Le patient participe à une autre étude.
• Le patient est en période d’exclusion déterminée par une étude précédente.
• Le patient est sous sauvegarde de justice, sous tutelle ou sous curatelle
• Le patient hors d'état d'exprimer leur consentement ne peuvent être sollicitées pour cette recherche (ex : personnes faisant l'objet de soins psychiatriques dont les troubles mentaux rendent impossible son consentement…)
• Le patient refuse de signer le consentement.
• Il s’avère impossible de donner au sujet des informations éclairées.
Critères de non-inclusion concernant les maladies ou conditions associé(e)s interférent(e)s :
• Patient ayant une maladie métastatique d’emblée.
• Contre-indication à la chirurgie
• Contre-indication à l’IRM (pacemaker non compatible IRM, claustrophobie, appareil métallique, prothèse totale de hanche).
• Patient avec antécédent de pontage aorto bifémoral ou autre chirurgie vasculaire condamnant l’accès endovasculaire aux artères prostatiques.
• Patient avec trouble de l’hémostase non réversible : TP < 50%, TCA > 2 fois le témoin, Plaquette < 60 G/L.

E.5 End points

E.5.1

Primary end point(s)

Number of serious adverse events with non-target necrosis type evaluated at D8 the day after embolization (clinical examination for non-target necrosis: severe bladder or rectal pain, rectorragy or abundant hematuria, fever) then D12 (by telephone) and D21, 2 weeks after embolization by MRI (bladder or rectal necrosis, fistula, abscess) and during surgery. Collection of complications at D30 post-operatively and M3

Nombre d’effets indésirables graves à type de nécrose non cible évalué à J8, le lendemain de l’embolisation (examen clinique à la recherche de nécrose non cible : douleur intense vésicale ou rectale, rectorragie ou hématurie abondante, fièvre) puis J12 (par téléphone) et J21, soit 2 semaines après l’embolisation par IRM (nécrose vésicale ou rectale, fistule, abcès) et lors de la chirurgie. Recueil des complications à J30 post-opératoire et M3

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

- MRI examination 1, 5 or 3 Tesla of the prostate (multiparametric acquisition with T2 morphological sequence, functional in diffusion and dynamic injection of contrast agent) at D21, i.e. 2 weeks after embolization: volume modification, necrosis zone.
- Early post-operative complications during hospitalization: description and classification of Clavien-Dindo: haematomas, arterial wound with bleeding, bladder wound, rectal wound, wall abscess, deep abscess...
- Early follow-up of symptoms and functional consequences on 21 days, 14 days after embolization and before surgery: administration of IPSS, IIEF-6, EORTC-QLQ C30 questionnaires.
- A M1 and M3 after surgery: collection of adverse events classified as Clavien-Dindo
- A M1 and M3 after surgery, monitoring of symptoms and functional consequences: International Prostate Symtom Score (IPSS), Pad Test 24h, variation in erectile function score (IIEF-6), quality of life measured using the EORTC QLQ-C30 prostate module questionnaire.
B. Blood determination of doxorubicin the day after embolization before discharge from hospital.
C. Determination of blood PSA at D21 before surgery. Conduct an MRI examination at D21 (target modification (PiRads classification), target size reduction).
D. Anatomical-pathological examination of the operating room: total necrosis of the tumour, partial necrosis > 50% of the tumour volume, minimal necrosis < 50% of the tumour volume, absence of necrosis.
E. Determination of blood PSA at 1 month and 3 months post surgery and comparison with baseline.

- Examen IRM 1,5 ou 3 Tesla de la prostate (acquisition multiparamétrique avec séquence morphologique en T2, fonctionnelle en diffusion et injection dynamique de produit de contraste) à J21 soit 2 semaines après l’embolisation : modification de volume, zone de nécrose.
- Complications post-opératoires précoces en cours d’hospitalisation : descriptif et classification de Clavien-Dindo : hématomes, plaie artérielle avec saignement, plaie vésicale, plaie rectale, abcès de paroi, abcès profond…
- Suivi précoce des symptômes et des conséquences fonctionnelles à J21, 14 jours après l’embolisation et avant la chirurgie : administration des questionnaires IPSS, IIEF-6, EORTC-QLQ C30.
- A M1 et M3 après chirurgie : recueil des évènements indésirables classés Clavien-Dindo
- A M1 et M3 après chirurgie, suivi des symptômes et conséquences fonctionnelles : International Prostate Symtom Score (IPSS), Pad Test 24h, variation du score de la fonction érectile (IIEF-6), qualité de vie mesurée à l'aide du questionnaire EORTC QLQ-C30 module prostate.
B. Dosage sanguin de la doxorubicine le lendemain de l’embolisation avant la sortie d’hospitalisation.
C. Dosage de la PSA sanguine à J21 avant chirurgie. Réalisation d’un examen IRM à J21 (modification de la cible (classification PiRads), diminution de taille de la cible).
D. Examen anatomo-pathologique de la pièce opératoire : nécose totale de la tumeur, nécrose partielle > 50% du volume tumoral, nécrose minime < 50% du volume tumoral, absence de nécrose.
E. Dosage de la PSA sanguine à 1 mois et 3 mois post chirurgie et comparaison avec la baseline.

E.5.2.1

Timepoint(s) of evaluation of this end point

1,5 or 3 Tesla MRI examination of the prostate gland
- Early post-operative complications
- symptoms and functional consequences at 21 days, 14 days after embolization and before surgery
- A M1 and M3 after surgery: collection of adverse events classified as Clavien-Dindo
- M1 and M3 after surgery, symptom follow-up, Score (IPSS), Pad Test 24h, (IIEF-6), EORTC QLQ-C30 prostate module.
B. Blood determination of doxorubicin the day after embolization
C. Blood PSA at D21 before surgery. MRI examination at D21 (target modification)
D. Anatomical-pathological examination of the operating part: total tumour necrosis, partial necrosis > 50% of the tumour volume, minimal necrosis < 50% of the tumour volume,
E. Blood PSA at 1 month and 3 months post surgery

Examen IRM 1,5 ou 3 Tesla de la prostate
- Complications post-opératoires précoces
- symptômes et des conséquences fonctionnelles à J21, 14 jours après l’embolisation et avant la chirurgie
- A M1 et M3 après chirurgie : recueil des évènements indésirables classés Clavien-Dindo
- M1 et M3 après chirurgie, suivi symptômes, Score (IPSS), Pad Test 24h, (IIEF-6), EORTC QLQ-C30 module prostate.
B. Dosage sanguin de la doxorubicine le lendemain de l’embolisation
C. PSA sanguine à J21 avant chirurgie. examen IRM à J21 (modification de la cible
D. Examen anatomo-pathologique de la pièce opératoire : nécrose totale de tumeur, nécrose partielle > 50% du volume tumoral, nécrose minime < 50% du volume tumoral,
E. PSA sanguine à 1 mois et 3 mois post chirurgie

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

Yes

E.6.6

Pharmacokinetic

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

E.8.2.2

Placebo

E.8.2.3

Other

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

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

The end of the trial will be the date of freeze of database

La fin de l'essai sera la date de gel de la base de données.

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

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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.4.2.2

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

Aucun

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

2020-03-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-12-03

P. End of Trial
P.	End of Trial Status	Ongoing

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