Clinical Trials Register

Summary
EudraCT Number:	2011-004686-32
Sponsor's Protocol Code Number:	v2.0
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2014-06-19
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

Netherlands - Competent Authority

A.2

EudraCT number

2011-004686-32

A.3

Full title of the trial

A Phase III double-blind placebo-controlled Randomised Trial of Aspirin on Recurrence and Survival in Colon Cancer Patients

De rol van aspirine op de overleving van patienten met dikkedarmkanker; een fase III dubbel blinde placebo gecontroleerde gerandomiseerde studie

A.3.1

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

The role of aspirin vs placebo on recurrence and survival in colon cancer patients

De rol van aspirine op de overleving van patienten met dikkedarmkanker

A.3.2

Name or abbreviated title of the trial where available

ASPIRIN Trial

ASPIRIN trial

A.4.1

Sponsor's protocol code number

v2.0

A.5.4

Other Identifiers

Name:

Nederlands Trial Register

Number:

NTR3370

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	Leiden University Medical Center
B.1.3.4	Country	Netherlands
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	Innovatiefonds Zorgverzekeraars
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	NutsOhra
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	Private donation
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Leiden University Medical Center
B.5.2	Functional name of contact point	Study coordinator
B.5.3	Address:
B.5.3.1	Street Address	P.O. box 9600
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2300 RC
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031715265890
B.5.6	E-mail	m.a.frouws@lumc.nl

D. IMP Identification
D.IMP: 1
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	Aspirine
D.2.1.1.2	Name of the Marketing Authorisation holder	Pharmachemie BV
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Aspirin
D.3.4	Pharmaceutical form	Tablet
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.3.9.3	Other descriptive name	ACETYLSALICYLIC ACID
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	80
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	Tablet
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

Patients must have TNM stage that is one of the following: pT3-4; N0-2 and M0, or pT1-2 and N1-2 (UICC stage II and III) (in case of >1 tumour: largest tumour is stage II or III)

Patiënten moeten een van de volgende pathologische stadia hebben: pT3-4; N0-2 en M0, of pT1-2 en N1-2 (UICC stadium II en III) (in het geval van >1 tumor: grootste tumor is stadium II of III)

E.1.1.1

Medical condition in easily understood language

Colon cancer

Dikkedarmkanker

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	LLT
E.1.2	Classification code	10009947
E.1.2	Term	Colon cancer Duke's B1
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10009948
E.1.2	Term	Colon cancer Duke's B2
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10009949
E.1.2	Term	Colon cancer Duke's C
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

To study effect of 80mg acetylsalicylic acid (given orally once daily for 5 years) on 5 year overall survival (OS) for stage II and III colon cancer patients of 45 years of age and older.

Het bestuderen van het effect van acetylsalicylzuur 80 mg (vijf jaar lang, eenmaal per dag) op de vijfjaarsoverleving voor stadium II en III coloncarcinoom patienten van 45 jaar en ouder.

E.2.2

Secondary objectives of the trial

-To study the effect of acetylsalicylic acid on 3 year disease free survival (DFS) in patients 45 years of age or older with stage II and III colon cancer.
-To study the effect of acetylsalicylic acid on time to treatment failure (TTF).
-To study the effect of acetylsalicylic acid on toxicity, for example the interaction of aspirin with chemotherapy.

-Het effect van acetylsalicylzuur op de drie jaar ziektevrije overleving in patienten van 45 jaar of ouder in stadium II en III colon carcinoom
-Effect van acetylsalicylzuur op tijd tot falen van de behandeling (Tijd tussen randomisatie en staken van de behandeling door ziekte terugkeer, onacceptabele toxiciteit, sterfte of elke andere significante gebeurtenis)
-Effect van acetylsalicylzuur op toxiciteit, bijvoorbeeld interactie tussen acetylsalicylzuur en chemotherapie

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Patients 45 years and older with histologically confirmed adenocarcinoma of the colon
-Patients must have TNM stage that is one of the following: pT3-4; N0-2 and M0, or pT1-2 and N1-2 (UICC stage II and III) (in case of >1 tumour: largest tumour is stage II or III)
-Patients must have completed surgical resection (R0) (both laparoscopic and open surgery) within 12 weeks of randomisation
-Written informed consent

-Leeftijd 45 jaar en ouder met histologisch bevestigd adenocarcinoom van de dikke darm
-Patiënten moeten een van de volgende pathologische stadia hebben: pT3-4; N0-2 en M0, of pT1-2 en N1-2 (UICC stadium II en III) (in het geval van >1 tumor: grootste tumor is stadium II of III)
-Patiënten die curatieve radicale resectie hebben ondergaan van de tumor binnen 12 weken voor het begin van de studie
-Voor randomisatie dient schriftelijke toestemming door de patiënt gegeven te worden

E.4

Principal exclusion criteria

-Patients with rectal cancer (defined as tumour within 15 cm from the anal verge)
-Patients currently taking oral anti-coagulants or use of LMWH
-Patients currently taking acetylsalicylic acid for any reason
-Patients with a history of bleeding disorders or active gastric or duodenal ulcers
-Patients currently taking high dose systemic glucocorticoids.(≥ 30 mg predniso(lo)n)
-Patients with (suspected) (non-) polyposis syndrome (FAP/AFAP, MAP, Lynch syndrome)
-Patients with >100 polyps of the colon or a known hereditary syndrome of the colon in a first degree family member
-Allergy or intolerance to salicylates.
-Patients with a history of other malignancies in the last 5 years, except for SCC or CIN.
-Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

-Patiënten met een rectum carcinoom (gedefinieerd als een tumor binnen 15 cm vanaf de anus)
-Patiënten die orale antistolling gebruiken of gebruik van low-molecular-weight heparin (LMWH).
-Patiënten die reeds aspirine, ascal of acetylsalicylzuur gebruiken
-Patiënten met stollingsstoornissen of actieve maag-of darmulcera
-Patiënten die momenteel een hoge dosering systemische glucocorticoïden gebruiken. (≥ 30 mg predniso(lo)n)
-Patienten met (verdenking) (non-) polyposis syndroom (FAP/AFAP, MAP, Lynch syndroom)
-Patiënten met >100 poliepen aan de dikkedarm of een bekend erfelijk syndroom van de dikkedarm in een eerste graads familielid
-Allergie of intolerantie voor aspirine
-Voorgeschiedenis van maligniteiten korter dan vijf jaar geleden, behoudens huidtumoren (CIN of BCC)
-Aanwezigheid van psychologische, familiaire, sociologische en/of geografische factoren die mogelijk invloed hebben op het naleven van de studie afspraken door de patiënt en het vervolgen van de studie

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of the trial is 5 year Overall Survival (5-yr OS).

Effect van acetylsalicylzuur op de 5-jaars overall survival (OS) bij patiënten 45 jaar of ouder met dikke darmkanker.

E.5.1.1

Timepoint(s) of evaluation of this end point

5 years

5 jaar

E.5.2

Secondary end point(s)

-Het effect van aspirine op de drie jaar ziektevrije overleving in patienten van 45 of ouder in stadium II en III colon carcinoom
-Effect van acetylsalicylzuur op tijd tot falen van de behandeling (Tijd tussen randomisatie en staken van de behandeling door ziekte toename, onacceptabele toxiciteit, sterfte of elke andere significante gebeurtenis)
-Effect van acetylsalicylzuur op toxiciteit, bijvoorbeeld interactie tussen aspirine en chemotherapie

E.5.2.1

Timepoint(s) of evaluation of this end point

3 years

3 jaar

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

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

The study will be terminated when there is one of the following criteria:
-Serious adverse side effects related only to acetylsalicylic acid use in >5 % of the subjects
-If the results of the interim analysis do not show survival benefit for acetylsalicylic acid use or if these results show a survival gain for control group.
OR LVLS

De studie zal vroegtijdig beëindigd worden op basis van de volgende criteria:
- Ernstige bijwerkingen gerelateerd aan acetylsalicylzuur gebruik bij meer dan 5% van de proefpersonen
- Als de resultaten van de interim analyse geen betere overleving geven voor de acetylsalicylzuur gebruikers of als de resultaten een betere overleving laten zien voor de controle groep
Of: laatste bezoek van de laatste proefpersoon.

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:

750

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

838

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

1588

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

Geen

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-06-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-08-05

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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