Clinical Trials Register

Summary
EudraCT Number:	2014-000411-14
Sponsor's Protocol Code Number:	1.1.1
National Competent Authority:	Finland - Fimea
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-10-11
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

Finland - Fimea

A.2

EudraCT number

2014-000411-14

A.3

Full title of the trial

A randomised double blind dose non-inferiority trial of a daily dose of 600mg versus 300mg versus 100mg of enteric coated aspirin as a cancer preventive in carriers of a germline pathological mismatch repair gene defect, Lynch Syndrome. Project 3 in the Cancer Prevention Programme (CaPP3).

A.3.1

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

CAPP3Fi

CAPP3FI

A.4.1

Sponsor's protocol code number

1.1.1

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN16261285

A.5.4

Other Identifiers

Name:

EudraCT

Number:

2014-000411-14

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	Mecklin Jukka-Pekka
B.1.3.4	Country	Finland
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Mecklin Jukka-Pekka
B.5.2	Functional name of contact point	Mecklin Jukka-Pekka
B.5.3	Address:
B.5.3.1	Street Address	KSSHP, Keskussairaalantie 19
B.5.3.2	Town/ city	Jyväskylä
B.5.3.3	Post code	40620
B.5.3.4	Country	Finland
B.5.4	Telephone number	358503615921
B.5.6	E-mail	jukka-pekka.mecklin@ksshp.fi

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	aspirin
D.2.1.1.2	Name of the Marketing Authorisation holder	bayer
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Coated 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	AS1
D.3.9.4	EV Substance Code	SUB12730MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	300
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ACETYLSALICYLIC ACID
D.3.9.4	EV Substance Code	SUB12730MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	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	Yes
D.3.11.13.1	Other medicinal product type	Placebo will be added to maintain dose blinding

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	Coated 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

Lynch Syndrome also known as HNPCC (non hereditary non polyposis colorectal cancer).

E.1.1.1

Medical condition in easily understood language

An inherited disorder that increases the risk of many types of cancer, particularly cancers of the colon (large intestine) and rectum, and also other cancers.

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10051981
E.1.2	Term	Lynch syndrome
E.1.2	System Organ Class	100000004850

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 find out which daily dose of Aspirin, 600mg or 300mg or 100mg, taken for 2 years is best at preventing cancers in patients with lynch syndrome. We will measure this by comparing the total number of Lynch Syndrome cancers (cancers that people with lynch syndrome are more likely to get) after a minimum of 5 years from study entry.

E.2.2

Secondary objectives of the trial

• Compare overall primary colorectal cancers in the three treatment groups
• Compare overall primary endometrial cancers in the three treatment groups.
• Compare overall cancers of all types,in the three treatment groups.
• Compare the burden of adverse events in three treatment groups.
. compare levels of antibodies against abnormal proteins released by Lynch Syndrome cancers.
• Through a linked biobanking strategy:
a)Identify reliable markers in the blood that predict future cancer development. This will help establish other cancer prevention strategies.
b)Help identify the likely mechanism of action on tumour formation.
c)Identify the influence of individual variability in aspirin metabolism

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age over 18
2. Proven MMR gene defect carrier
3. CAPP2 participants, at least 10 years since enrolled into that study
4. Willing to take randomised blinded dose (100, 300, 600mg) of aspirin for two years & self-report numbers of tablets taken
5. Agreement for indefinite clinical follow up with a minimum of 5 years
6. Availability of Micro satellite instability and or immunohistochemical analysis of mismatch repair proteins to establish whether any lesions are likely to be Lynch syndrome related, are all non-negotiable
7. Biobanking (bloods for DNA & serum) and sharing tissue sections to allow pharmacogenetic sub studies, FSP(Frame shift peptide) antibody testing and effects of aspirin on molecular tumour phenotype are desirable but not essential

E.4

Principal exclusion criteria

1. Regular use of a non-steroidal anti-inflammatory agent (except aspirin) on a
prescription and/or long-term basis. Regular is defined as > 3 doses per week.
2. Regular use of aspirin (> 3 doses per week or on a prescription basis) that cannot be replaced with any one of the randomised arms of the study followed by 100mg dose.
3. Current methotrexate use.
4. Known aspirin intolerance or hypersensitivity, including aspirin-sensitive asthma.
5. Existing clinically significant liver impairment.
6. Existing renal failure defined as creatinine clearance <10ml/min.
7. Active peptic ulcer disease within the previous three months or any previous proven peptic ulcer.
8. Known bleeding diathesis or concomitant warfarin therapy.
9. Inability to comply with study procedures and agents.
10. Women reporting that they are pregnant or actively planning to achieve a pregnancy within the next two years.
11. Women who are currently breastfeeding.
12. Any significant medical illness that would interfere with study participation.
13. Previous participation in this trial. [Participation in the previous CAPP2 study will not exclude patients from this study. The protocol requires that it be at least 10 years since they joined CAPP2. Recruitment to CAPP2 closed in 2006].

E.5 End points

E.5.1

Primary end point(s)

The number of new primary mismatch repair deficient cancers (“Lynch syndrome cancers”) at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years

E.5.1.1

Timepoint(s) of evaluation of this end point

Five years after last recruit enters trial

E.5.2

Secondary end point(s)

• The number of new colorectal cancers at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years.
• The number of new endometrial cancers at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years.
• The number of new cancers of all types at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years.
• Changes at 2 & 5 years in the titre of frameshift peptide antibodies from commencement of the prescribed treatment.

E.5.2.1

Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

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

Yes

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

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

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

End of study is defined as five years from randomisation of the last 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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

300

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

300

F.4.2

For a multinational trial

F.4.2.1

In the EEA

3000

F.4.2.2

In the whole clinical trial

3000

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)

There is no continued provision for intervention for patients after the 7 year study

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

2016-11-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-01-16

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

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