Finding the best dose of aspirin to prevent Lynch Syndrome cancers

ISRCTN	ISRCTN16261285
DOI	https://doi.org/10.1186/ISRCTN16261285
EudraCT/CTIS number	2014-000411-14
IRAS number	141927
ClinicalTrials.gov number	NCT02497820
Secondary identifying numbers	17122

Submission date: 14/10/2015
Registration date: 14/10/2015
Last edited: 11/10/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

http://www.cancerresearchuk.org/about-cancer/trials/a-trial-looking-at-different-doses-of-aspirin-to-prevent-cancer-in-people-with-lynch-syndrome-capp3

Study website

Contact information

Dr John Burn
Public

Institute of Human Genetics
International Centre For Life
Central Parkway
Newcastle Upon Tyne
NE1 3BZ
United Kingdom

Phone	+44 191 241 8613
Email	john.burn@ncl.ac.uk

Dr . Study Team
Scientific

Institute of Human Genetics
International Centre For Life
Central Parkway
Newcastle Upon Tyne
NE1 3BZ
United Kingdom

Email	CaPP3@ncl.ac.uk

Study information

Study design	Randomised; Interventional; Design type: Screening, Treatment
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Other
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	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).
Study acronym	CaPP3
Study hypothesis	The aim of this study is to find the most effective dose of aspirin for people with a mismatch repair gene defect, the underlying cause of Lynch syndrome.
Ethics approval(s)	Approved 15/05/2014, NRES Committee North East - Newcastle & North Tyneside 2 (Health Research Authority Ground Floor, Skipton House, 80 London Road, London, SE1 6LH, United Kingdom; no telephone number provided; newcastlenorthtyneside2.rec@hra.nhs.uk), ref: 14/NE/0103
Condition	Lynch syndrome
Intervention	Participants are asked to take three tablets each day for two years. One tablet will be a placebo, and at least one of the tablets will contain enteric coated aspirin at a dose of either 100mg, 300mg or 600mg. After 2 years on the blinded dose, participants will be given 100mg open label enteric coated aspirin until the last recruit reaches their fifth anniversary. Drug packs will be delivered directly to the patient to save them travelling to collect the drug. They will be routinely followed up by an initial phone call at 3 months and then 6 monthly thereafter for the blinded phase. In the open label phase only yearly follow ups will be required. The aim is to balance adequate safety follow up whilst remaining mindful that patients are not “sick”, so minimising travelling to hospital and being in a clinical environment unnecessarily.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Aspirin
Primary outcome measure	The frequency of Lynch Syndrome Cancers is determined throughout the study and during 10 years following the end of the study.
Secondary outcome measures	Not provided at time of registration
Overall study start date	01/10/2014
Overall study end date	15/07/2024

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 3000; UK Sample Size: 750; Description: As the NHS in the UK are not permitted to sponsor studies overseas, we are encouraging colleagues in other countries to replicate our design exactly which will allow us to pool data. If this is successful we estimate the UK contribution will be 750-1500, with most of the rest coming from EU countries and Australia. All overseas investigatorsrunning parallel studies are responsible for satisfying all their own countries' ethical and regulatory processes.
Total final enrolment	1567
Participant inclusion criteria	1. Aged 18 years or over 2. Confirmed germline pathological variant in one of the mismatch repair genes: MSH2, MLH1, PMS2 or MSH6 or a 3’ EPCAM deletion associated with MSH2 silencing or be a carriers of a constitutional epimutation manifesting a classic Lynch syndrome phenotype 3. Able to swallow tablets 4. Willing to complete the CaPP3 consent process as described in the patient information sheet
Participant 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. Known aspirin intolerance or hypersensitivity, including aspirin-sensitive asthma 4. Existing clinically significant liver impairment 5. Existing renal failure 6. Confirmed active peptic ulcer disease within the previous three months 7. Known bleeding diathesis or concomitant anticoagulant therapy 8. Inability to comply with study procedures and agents 9. Women reporting that they are pregnant or actively planning to achieve a pregnancy within the next two years 10. Women who are breastfeeding 11. Any significant medical illness that would interfere with study participation. (If hypertension is discovered, the participant should be advised to have this treated before commencing trial medication) 12. Participation in the previous CAPP2 study will not exclude patients from this study, apart from the small number recruited less than 10 years previously Previous use of aspirin for medicinal purposes does not exclude enrollment but duration and quantity need to be documented in detail.
Recruitment start date	01/10/2014
Recruitment end date	31/03/2019

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Institute of Human Genetics

International Centre For Life
Central Parkway
Newcastle Upon Tyne
NE1 3BZ
United Kingdom

Sponsor information

Newcastle upon Tyne Hospitals NHS Foundation Trust
Hospital/treatment centre

Institute of Genetic Medicine
International Centre for Life
Central Parkway
Newcastle upon Tyne
NE1 3BZ
England
United Kingdom

"ROR"	https://ror.org/05p40t847

Funders

Funder type

Charity

Cancer Research UK
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Bayer Pharmaceuticals Plc.

No information available

Results and Publications

Intention to publish date	31/08/2025
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Planned publication in a peer-reviewed journal
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No

Editorial Notes

11/10/2024: The following changes were made to the trial record:
1. The public contact was changed.
2. The scientific contact was added.
3. The IRAS number was added.
4. The overall end date was changed from 31/08/2024 to 15/07/2024.
5. The total final enrolment was added.
08/04/2024: ClinicalTrials.gov number added.
19/08/2021: The following changes were made to the trial record:
1. The overall end date was changed from 31/08/2021 to 31/08/2024.
2. The intention to publish date was added.
04/05/2020: The recruitment end date has been changed from 31/08/2021 to 31/03/2019.
03/04/2019: The condition has been changed from "Topic: Cancer, Genetics; Subtopic: All Cancers/Misc Sites, Genetics Research and Congenital Disorders (all subtopics); Disease: All, Genetics Research and Congenital Disorders" to "Lynch syndrome" following a request from the NIHR.