Clinical Trials Register

Summary
EudraCT Number:	2016-002209-20
Sponsor's Protocol Code Number:	2015/222/HP
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:	2016-11-22
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

2016-002209-20

A.3

Full title of the trial

PRODIGE 50 - ASPIK : French prospective randomised double blind study on aspirin versus placebo in resected colon cancer with PI3K mutation stage III or II high risk

PRODIGE 50 - ASPIK: Etude prospective randomisée en double aveugle aspirine versus placebo chez les patients opérés d’un adénocarcinome du colon stade III ou II à haut risque de récidive avec mutation PI3K.

A.3.1

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

Evaluation of the efficacy of low-dose aspirin on the recurrence of the disease in people recently operated for colon cancer

Evaluation de l’efficacité de l’aspirine à faible dose sur la récidive de la maladie chez les personnes opérées récemment d’un cancer du côlon

A.3.2

Name or abbreviated title of the trial where available

PRODIGE 50 - ASPIK FRENCH

A.4.1

Sponsor's protocol code number

2015/222/HP

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-Hôpitaux de Rouen
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	INCA 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	Fédération Francophone de Cancérologie Digestive (FFCD)
B.5.2	Functional name of contact point	Jérémie BEZ
B.5.3	Address:
B.5.3.1	Street Address	7 Boulevard Jeanne d'Arc
B.5.3.2	Town/ city	DIJON
B.5.3.3	Post code	21079
B.5.3.4	Country	France
B.5.4	Telephone number	33380393483
B.5.5	Fax number	33380381841
B.5.6	E-mail	jeremie.bez@u-bourgogne.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	ASPIRINE PROTECT 100 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	BAYER 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	Pillules
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ACETYLSALICYLIC ACID
D.3.9.1	CAS number	50-78-2
D.3.9.4	EV Substance Code	SUB12730MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Pillules
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Mutated PI3K colonic adenocarcinoma patients with surgical resection R0

Patient atteint d'un adenocarcinome du colon Pi3K muté avec résection chirurgicale R0

E.1.1.1

Medical condition in easily understood language

Patient with colon cancer with a mutated gene (PI3K) which has been completely removed by surgery

Patient présentant un cancer du colon avec un gène muté (gène PI3K) qui a totalement été retiré par chirurgie

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to assess the effectiveness of aspirin on the disease-free survival at 3 years after curative surgery for colonic adenocarcinoma with PI3K mutation.

Evaluer l’efficacité de l’aspirine sur la survie sans maladie à 3 ans après chirurgie curative d’un adénocarcinome du côlon avec une mutation PI3K.

E.2.2

Secondary objectives of the trial

- Disease-free survival at 5 years
- Overall survival at 5 years
- Compliance to aspirin (Thromboxane B2 measurements and comptability of containers)
- Severe bleeding grade 3-4 events and hospitalization according to NCI-CTC grading 4.0
- Adverse event reported and graded according to NCI-CTC grading 4.0

- Survie sans maladie à 5 ans
- Survie globale à 5 ans
- Compliance à l’aspirine (dosage de TxB2 sanguin + comptabilité des comprimés)
- Hémorragie sévère grade 3-4 (hospitalisation) selon la classification NCI-CTC grade 4.0
- Evènement indésirable grave selon la classification NCI-CTC version 4.0

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

A large biobank of blood of patients with resected colon cancer with PI3K mutations, as a basis for translational research projects. The research projects planned include the identification of circulant tumoral DNA and the quantification of tumoral DNA in blood, every 6 months, during the follow-up.

E.3

Principal inclusion criteria

1. Age ≥ 18 years
2. Colonic adenocarcinoma stage III
3. Colonic adenocarcinoma stage II high risk MSS:
a. T4bN0 or T4a tumour penetrating the surface of the visceral peritoneum;
b. or less than 12 nodes evaluated;
c. or with at least two of the following criteria: lymphatic involvement, perineural invasion, venous invasion; or diagnosis of bowel obstruction or perforation; or poor differentiated tumour).
4. PI3K mutation, exon 9 or 20 (tumour)
5. Resection R0
6. WHO performance status 0-2
7. Chest and abdominal CT scan ≤ 8 weeks
8. Life expectancy ≥ 3 years
9. Written consent signed

- Age ≥ 18 ans
- Adénocarcinome du côlon de stade III
- Adénocarcinome Stade II à haut risque MSS
o T4bN0 or T4aN0 tumeur pénétrant la surface du péritoine viscéral
o ou moins de 12 ganglions examinés
o ou au moins deux des critères suivants : envahissement lymphatique, invasion péri-nerveuse, invasion veineuse ; ou diagnostic sur syndrome occlusif ou sur une perforation ; ou tumeur peu différenciée).
- mutation PI3K, exon 9 ou 20 (tumeur)
- Résection R0
- OMS 0-2
- Tomodensitométrie thoracique et abdominale datant de moins de 8 semaines.
- Espérance de vie ≥ 3 an
- Consentement écrit signé

E.4

Principal exclusion criteria

1. Anticoagulant and/or Antiaggregating treatment including clopidogrel
2. Regular aspirin use (> 3 doses per week during more than 3 months the last year)
3. Follow-up of the patient not feasible
4. Contraindication to Aspirin :
a. Active or antecedent peptic ulcer
b. Allergy to aspirin
5. Severe renal or hepatic insufficiency
6. Pregnancy or nursing ongoing
7. Rectal cancer
8. Hereditary forms (i.e. lynch syndrome patients)

- Traitement anticoagulants et/ou anti agrégants incluant le clopidogrel
- Consommation d’aspirine régulière (plus de 3 prises par semaine pendant au moins 3 mois pendant la dernière année)
- Contre-indication à l’aspirine : Allergie à l ‘aspirine, Antécédent d’ulcère gastroduodénal
- Insuffisance hépatique ou rénale sévère
- Femme enceinte ou allaitante
- Cancer du rectum
- Forme héréditaire (i.e. syndrome de Lynch)
- Suivi impossible

E.5 End points

E.5.1

Primary end point(s)

The objective is to demonstrate a reduction of 44% on the disease-free survival(DFS) rate at 3 years. DFS is defined as the time from date of randomization to date of first local or distant recurrence, or second colorectal cancer, or death (from any cause), whichever occurred first.

E.5.1.1

Timepoint(s) of evaluation of this end point

3 years after the inclusion of the last patient

3 ans après l'inclusion du dernier patient

E.5.2

Secondary end point(s)

Secondary endpoints are :
- Disease-free survival at 5 years
- Overall survival at 5 years
- Compliance to aspirin (Thromboxane B2 measurements and comptability of containers)
- Severe bleeding grade 3-4 events and hospitalization according to NCI-CTC grading 4.0
- Adverse event reported and graded according to NCI-CTC grading 4.0

Les obectifs secondaires sont:
- Survie sans maladie à 5 ans
- Survie globale à 5 ans
- Compliance à l’aspirine (dosage de TxB2 sanguin + comptabilité des comprimés)
- Hémorragie sévère grade 3-4 (hospitalisation) selon la classification NCI-CTC grade 4.0
- Evènement indésirable grave selon la classification NCI-CTC version 4.0

E.5.2.1

Timepoint(s) of evaluation of this end point

5 years after the inclusion of the last patient

5 ans après l'inclusion du dernier patient

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

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)

E.8.2.2

Placebo

Yes

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

lvls

Dernière visite du dernier patient

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:

102

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

264

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

2017-10-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-07-02

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

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