Clinical Trials Register

Summary
EudraCT Number:	2011-004406-25
Sponsor's Protocol Code Number:	UC-0110/1005
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:	2011-10-07
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

2011-004406-25

A.3

Full title of the trial

Etude randomisée de phase III comparant une radiochimiothérapie préopératoire à une chimiothérapie néoadjuvante Folfirinox suivie de radiochimiothérapie préopératoire pour les patients atteints de cancers du rectum localement avancés (étude PRODIGE-GERCOR-SFRO-GRECCAR)

A.3.2

Name or abbreviated title of the trial where available

NEOFIRINOX

A.4.1

Sponsor's protocol code number

UC-0110/1005

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	UNICANCER
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	PHRC
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	UNICANCER
B.5.2	Functional name of contact point	Nourredine AIT-RAHMOUNE
B.5.3	Address:
B.5.3.1	Street Address	101, rue de Tolbiac
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75013
B.5.3.4	Country	France
B.5.4	Telephone number	01 71 93 67 04
B.5.5	Fax number	01 53 79 02 90
B.5.6	E-mail	n.a-rahmoune@unicancer.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	ELOXATINE
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI-AVENTIS 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	OXALIPLATINE
D.3.4	Pharmaceutical form	Solution for injection/concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous 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.2.1.1.1	Trade name	CAMPTO
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	IRINOTECAN
D.3.4	Pharmaceutical form	Solution for injection/concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous 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: 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.2.1.1.1	Trade name	ELVORINE
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	ACIDE FOLINIQUE
D.3.4	Pharmaceutical form	Powder and solution for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous 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: 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	5-FLUOROURACIL
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI AVENTIS 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	5-FLUOROURACILE
D.3.4	Pharmaceutical form	Powder and solution for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous 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

Adénocarcinome du rectum

E.1.1.1

Medical condition in easily understood language

Cancer du rectum

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	14.0
E.1.2	Level	PT
E.1.2	Classification code	10038038
E.1.2	Term	Rectal cancer
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 maladie à 3 ans entre les 2 bras.

E.2.2

Secondary objectives of the trial

-Evaluer la survie globale et la survie spécifique
-Evaluer les toxicités maximales par patient (grade 3-4) selon la classification NCI-CTC v4.0 au cours de chaque période de traitement
-Evaluer le taux de récidives locales
-Evaluer le taux de récidives métastatiques, déduit de la survie sans métastases
-Taux de stérilisation de la pièce opératoire (ypT0N0)
-Evaluer la qualité de l’exérèse (chirurgie R0)
-Taux de morbidité opératoire
-Recherche translationnelle (optionnelle).
-Qualité de vie (étude satellite optionnelle)

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

1/ Sur tumeur : pharmaco-génomique

•Conservation d’échantillons (tissu, protéines et ADN) en vue de travaux de recherche ultérieurs et pour identifier par la génomique le risque métastatique précoce.
•Etude de la valeur pronostique de l’instabilité des microsatellites.

2/ Sur prélèvements sanguins : pharmacogénétique

Recherche de Single Nucleotide Polymorphisms (SNP) sur puce Illumina 15000 SNP pour identifier des polymorphismes génétiques prédictifs de la toxicité et de la réponse au Folfirinox néoadjuvant et à la RCT préopératoire, parmi les 600 gènes codant des protéines impliquées dans :

•métabolisme / transport des médicaments, notamment DPYD en relation avec la toxicité hématologique du 5FU et UGT1A1 en relation avec la toxicité de l’irinotécan,
•réparation de l’ADN, notamment ERCC1 en relation avec la réponse à l’oxaliplatine,
•apoptose,
•angiogenèse / lymphangiogenèse.

E.3

Principal inclusion criteria

1)Adénocarcinome du rectum classé cT3 à risque de récidive locale ou cT4, M0 et pour lequel une RCP recommande une radiochimiothérapie préopératoire
2)Tumeur ≤15 cm de la marge anale en rectoscopie rigide ou sous-péritonéale à l’IRM
3)Tumeur potentiellement résécable d’emblée, ou considérée comme pouvant être résécable après radiochimiothérapie
4)Patient opérable
5)Patient de 18 à 75 ans
6)Etat général : OMS 0-1
7)Pas de comorbidité susceptible d’empêcher la délivrance du traitement
8)Contraception adéquate pour les hommes, et pour les femmes non ménopausées. Les patients en âge de procréer doivent accepter d’utiliser deux méthodes de contraception validées médicalement (une pour le patient et l’autre pour le partenaire) durant l’étude et durant les 6 mois pour les hommes et 4 mois pour les femmes suivant la dernière prise de traitement
9)Polynucléaires neutrophiles ≥ 1500/mm3, plaquettes≥ 100 000/mm3, et hémoglobine ≥ 10 g/dL - éventuellement après transfusions)
10)Bilirubine normale
11)Clairance à la créatinine > 50 mL/mn (clairance estimée)
12)Information du patient et signature du consentement éclairé
13)Affiliation à un régime de sécurité sociale

E.4

Principal exclusion criteria

1)Métastases à distance
2)Cancer non résécable, dont extension prostatique ou extension aux muscles périnéaux
3)Contre-indication au 5-FU, ou à l’oxaliplatine ou à l’irinotécan, dont maladie de Gilbert connue
4)Neuropathie périphérique > grade 1
5)Antécédent de radiothérapie pelvienne ou de chimiothérapie antérieure
6)Antécédents de maladie inflammatoire du côlon ou du rectum
7)Antécédents d’angine de poitrine même contrôlée ou d’infarctus du myocarde ou d’insuffisance cardiaque
8)Infection évolutive active ou autre pathologie grave sous-jacente susceptible d’empêcher le patient de recevoir le traitement
9)Autre cancer concomitant, ou antécédent de cancer en dehors d’un cancer in situ du col utérin traité ou d’un carcinome basocellulaire ou spinocellulaire
10)Patient déjà inclus dans un autre essai thérapeutique avec une molécule expérimentale
11)Femme enceinte, susceptible de l’être, ou en cours d'allaitement
12)Intolérance connue au fructose
13)Traitement par la sorivudine ou analogues (brivudine)
14)Personnes privées de liberté ou sous tutelle
15)Impossibilité de se soumettre au suivi médical de l'essai pour des raisons géographiques, sociales ou psychiques

E.5 End points

E.5.1

Primary end point(s)

Démontrer un gain de 10% de survie sans maladie

E.5.1.1

Timepoint(s) of evaluation of this end point

6 ans

E.5.2

Secondary end point(s)

-Le taux de patients n’ayant eu aucune chirurgie d'exérèse rectale (simple colostomie exclue) dans le bras expérimental par rapport au bras standard,
-Le taux de réhospitalisations postopératoires pour quelque raison que ce soit (hors hospitalisation pour CT adjuvante) dans le bras expérimental par rapport au bras standard

E.5.2.1

Timepoint(s) of evaluation of this end point

Après l’inclusion de 100 patients dans chaque bras.

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

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Questionnaires de qualité de vie QLQ-CR29

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

Yes

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)

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

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

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

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.1.3

Elderly (>=65 years)

Yes

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

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

460

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)

A l'issue de la surveillance prévue dans le cadre de cette étude, la surveillance se fera en fonction des pratiques médicales du centre investigateur.

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

2011-12-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-12-06

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

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