Clinical Trials Register

Summary
EudraCT Number:	2014-005188-34
Sponsor's Protocol Code Number:	GORTEC2014-03
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:	2015-05-13
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

2014-005188-34

A.3

Full title of the trial

Phase III trial of laryngeal preservation comparating Induction chemotherapy with cisplatin, 5-fluorouracil and docetaxel (TPF) followed by radiotherapy and concomitant administration of radiotherapy with cisplatin.

Etude de phase III de préservation laryngée comparant une Chimiothérapie d’induction associant le Cisplatine, le 5-Fluorouracile et le Docétaxel (TPF) suivie de Radiothérapie à une Radiothérapie associée à l’administration de Cisplatine.

A.3.1

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

Phase III trial of laryngeal preservation comparating chemotherapy followed by radiotherapy to chemotherapy administrated during radiotherapy.

Etude de phase III de préservation laryngée comparant une Chimiothérapie première suivie de Radiothérapie à une chimiothérapie administrée pendant la radiothérapie.

A.3.2

Name or abbreviated title of the trial where available

SALTORL

A.4.1

Sponsor's protocol code number

GORTEC2014-03

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	GORTEC
B.1.3.4	Country	Switzerland
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	GORTEC
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	GORTEC
B.5.2	Functional name of contact point	Marie-Hélène GIRARD CALAIS
B.5.3	Address:
B.5.3.1	Street Address	Centre Henry Kaplan-CHU Bretonneau 2 Bd Tonnellé
B.5.3.2	Town/ city	Tours cedex 1
B.5.3.3	Post code	37044
B.5.3.4	Country	France
B.5.4	Telephone number	33(0)2 47 47 91 21
B.5.5	Fax number	33(0)2 34 38 94 11
B.5.6	E-mail	rc.corad@chu-tours.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	Cisplatine Accord
D.2.1.1.2	Name of the Marketing Authorisation holder	ACCORD HEALTHCARE FRANCE 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.3.1	Product name	CISPLATINE
D.3.4	Pharmaceutical form	Solution for infusion
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	CISPLATINE
D.3.9.3	Other descriptive name	CISPLATIN
D.3.9.4	EV Substance Code	SUB07483MIG
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	Comparator
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	Docetaxel Accord
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord Healthcare Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	DOCETAXEL
D.3.2	Product code	DOCETAXEL
D.3.4	Pharmaceutical form	Solution for infusion
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	DOCETAXEL
D.3.9.3	Other descriptive name	DOCETAXEL
D.3.9.4	EV Substance Code	SUB12492MIG
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	Comparator
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	Fluorouracile
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord Healthcare Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Fluorouracile
D.3.4	Pharmaceutical form	Solution for infusion
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	FLUOROURACILE
D.3.9.3	Other descriptive name	FLUOROURACIL
D.3.9.4	EV Substance Code	SUB07721MIG
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	Comparator
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	CISPLATINE ACCORD
D.2.1.1.2	Name of the Marketing Authorisation holder	ACCORD HEALTHCARE FRANCE 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.3.1	Product name	CISPLATINE
D.3.4	Pharmaceutical form	Solution for infusion
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	CISPLATINE
D.3.9.3	Other descriptive name	CISPLATIN
D.3.9.4	EV Substance Code	SUB07483MIG
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

carcinomes épidermoïdes du larynx ou de l’hypopharynx localement avancé

E.1.1.1

Medical condition in easily understood language

carcinomes épidermoïdes du larynx ou de l’hypopharynx localement avancé

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	18.0
E.1.2	Level	PT
E.1.2	Classification code	10060121
E.1.2	Term	Squamous cell carcinoma of head and neck
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Comparer la survie sans dysfonctionnement laryngé ou pharyngo-œsophagien 2 ans après la fin du traitement, obtenue par la trithérapie (TPF) suivie d’une radiothérapie externe ou par l’association concomitante de radiothérapie externe et de Cisplatine.

E.2.2

Secondary objectives of the trial

•Survie globale
•Survie sans récidive
•Contrôle locorégional
•Métastases à distance (incidence et survie)
•Préservation laryngée
•Taux de réponse à la chimiothérapie d’induction
•Toxicité aiguë et tardive
•Faisabilité et morbidité de la chirurgie de rattrapage
•Qualité de la fonction laryngée et pharyngo-œsophagienne
•Analyse des paramètres en fonction des critères de stratification

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Les patients ayant:
•Carcinome épidermoïde du larynx ou de l’hypopharynx (à l’exclusion de la région rétro-cricoaryténoïdienne et de la paroi postérieure), histologiquement prouvé, localement avancé relevant d’une (pharyngo)-laryngectomie totale à la condition que cette dernière soit réalisable d’emblée et ne nécessite pas une hypopharyngectomie circulaire :
- T2 non accessible à une laryngectomie partielle supra-cricoïdienne ou non,
- T3 sans infiltration massive de l’endolarynx par une lésion trans-glottique,
- N0 à N2c
- Sans métastase à distance
- Sans cancer associé, ni antérieur
•Patient non traité antérieurement
•Age > 18 ans et < 75 ans
•PS 0 ou 1 selon l’OMS
•Volume tumoral évaluable selon les critères RECIST.
•Absence de métastase à distance, confirmée par TDM thoracique, échographie abdominale (ou TDM) en cas d'anomalie de la fonction hépatique, et scintigraphie osseuse en cas de symptômes locaux.
•Absence de toute participation à un essai thérapeutique dans les 30 jours précédant l’inclusion.
•Absence de tout traitement anticancéreux concomitant.
•Absence de tout traitement chronique (* 3 mois) par corticoïde dont la posologie journalière est * 20 mg/jour de methylprednisolone ou équivalent.
•Fonctions hématologiques : neutrophiles * 1.5 x 109/l, plaquettes * 100 x 109/l, hémoglobine * 10 g/dl (ou 6,2 mmol/l).
•Fonction hépatique : bilirubine totale normale ; ASAT (SGOT) et ALAT (SGPT) * 2.5 * la limite supérieure normale (LNS) de chaque centre ; phosphatases alcalines * 5 * LNS.
•Fonction rénale : créatinine sérique * 120 *mol/l (1.4 mg/dl) ; si la créatinine est > 120 *mol/l, la clairance de la créatinine doit être * 60 ml/min.
•Espérance de vie supérieure ou égale à 3 mois
•Perte de poids inférieure à 10 % au cours des 3 derniers mois
•Questionnaires VHI et DHI
•Patient ayant donné son consentement écrit avant toute procédure spécifique du protocole.
•Les femmes et les hommes en âge de procréer doivent avoir accepté une contraception médicalement efficace pendant la durée du traitement e au moins pour les 3 mois suivant l’arrêt du traitement. Si une grossesse es déclarée par une patiente pu la partenaire d’un patient, elle doit être suivie pour connaître l’évolution de la grossesse.
•Vidéoscopie dynamique de la déglutition

E.4

Principal exclusion criteria

•T3 trans-glottique avec infiltration massive de l’hémilarynx ou T4 avec lyse cartilagineuse massive ou tumeur de la région rétro-cricoarythénoïdenne ou de la paroi hypopharyngée postérieure
•Tumeur nécessitant la réalisation d’une trachéotomie d’emblée.
•Tumeur accessible d’emblée à une chirurgie partielle.
•Tumeur nécessitant une hypopharyngectomie circulaire
•Lésion ganglionnaire N3
•Autre cancer antérieur ou concomitant, à l'exception d’un cancer in situ du col de l’utérus, d’un carcinome cutané (basocellulaire) ou cancer de la prostate contrôlé depuis plus de 3 ans. Les patients en rémission complète d’un cancer traité il y a plus de 5 ans peuvent être inclus dans l’étude.
•Les patients avec des ASAT ou ALAT > 1.5 * LNS associés à des phosphatases alcalines * 2.5 * LNS ne seront pas éligibles pour l’essai.
•Neuropathie périphérique symptomatique de grade * 2 selon les critères NCI-CTC.
•Altération clinique de la fonction auditive.
•Autres pathologies médicales sérieuses concomitantes (liste non exhaustive) :
-Pathologie cardiaque instable malgré traitement.
-Infarctus de myocarde dans les 6 mois précédant l’entrée dans l’essai.
-Antécédents neurologiques ou psychiatriques tels que démence, convulsions ;
-Infection sévère non contrôlée.
-Anomalies gastro-intestinales significatives, compris celles qui nécessitent une nutrition parentérale, ulcère gastroduodénal évolutif et antécédents d’interventions chirurgicales affectant l’absorption
-Broncho-pneumopathie obstructive ayant nécessité une hospitalisation dans l'année précédant l’inclusion.
-Diabète instable ou autres contre-indications aux corticostéroïdes.
-Anomalie ophtalmologique significative.
-Eczéma modéré ou sévère.
•Allergie à l’iode.
•Hypersensibilité au Docétaxel, au Cisplatine ou à l’un de leurs excipients.
•Utilisation concomitante de phénytoïne, carbamazépine, barbituriques ou rifampicine.
•Présence, à la sélection, de facteurs d’ordre psychologique, familial, social ou géographique susceptibles de modifier l’observance du patient avec le protocole à l’étude et le suivi, constitue un critère de non-inclusion. Ces facteurs doivent être discutés avec le patient avant inclusion dans l’essai.
•Femmes enceintes ou allaitant.
•Patient (homme ou femme) en âge de procréer ne prenant pas de mesures contraceptives adéquates

E.5 End points

E.5.1

Primary end point(s)

Survie à 2 ans sans événement carcinologique avec préservation de la fonction laryngée et pharyngo-œsophagienne

E.5.1.1

Timepoint(s) of evaluation of this end point

Une évaluation clinique de la survie sera faite à 24 mois par TDM et par vidéoscopie dynamique de la déglutition afin d'évaluer la fonction pharyngo-œsophagienne.

E.5.2

Secondary end point(s)

•Survie globale
•Survie sans récidive
•Contrôle locorégional
•Survie sans métastases et incidence des métastases
•Préservation laryngée
•Faisabilité et morbidité de la chirurgie de rattrapage
•Qualité de la fonction laryngée et pharyngo-œsophagienne

E.5.2.1

Timepoint(s) of evaluation of this end point

Une surveillance clinique sera faite tous les 3 mois pendant 2 ans, puis tous les 6 mois; évaluation faite par scanner en cas de doute

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

Yes

E.6.4

Safety

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

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.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

440

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

440

F.4.2

For a multinational trial

F.4.2.1

In the EEA

440

F.4.2.2

In the whole clinical trial

440

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

2015-04-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-01-27

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

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