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Trial registered on ANZCTR


Registration number
ACTRN12617000804381
Ethics application status
Approved
Date submitted
22/05/2017
Date registered
1/06/2017
Date last updated
23/08/2022
Date data sharing statement initially provided
9/05/2019
Date results information initially provided
22/04/2020
Type of registration
Retrospectively registered

Titles & IDs
Public 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.
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).
Secondary ID [1] 292008 0
Nil known
Universal Trial Number (UTN)
Trial acronym
CaPP3 Australia
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lynch Syndrome 303392 0
Cancer 303393 0
Condition category
Condition code
Human Genetics and Inherited Disorders 302806 302806 0 0
Other human genetics and inherited disorders
Cancer 302887 302887 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Enteric-coated aspirin 100mg, 300mg or 600mg blinded dose daily for a duration of 2 years.

Oral tablet, twice a day administration. Unused drug blister pack will need to be returned every 6 months for reconciliation and monitoring adherence.
Intervention code [1] 298138 0
Prevention
Intervention code [2] 298237 0
Treatment: Drugs
Comparator / control treatment
This is a dose comparison study between 100 mg, 300 mg and 600 mg of aspirin daily. There is no placebo involved.
Control group
Dose comparison

Outcomes
Primary outcome [1] 302188 0
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. Participants will be followed up to document whether a cancer has developed. In the event of a cancer, the primary physician will be consulted with to obtain further information and medical records reviewed.
Timepoint [1] 302188 0
Throughout the study (5 years) and for a ten year follow up period. Altogether 15 years.
Secondary outcome [1] 335135 0
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.
Through out the study participants will be followed up to document whether they have developed cancer. In the event of a cancer, relevant documentation will be obtained through their medical records and primary physician.
Timepoint [1] 335135 0
Throughout the study (5 years) and for a ten year follow up period. Altogether 15 years.
Secondary outcome [2] 335345 0
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.
Through out the study participants will be followed up to document whether they have developed cancer. In the event of a cancer, relevant documentation will be obtained through their medical records and primary physician.

Timepoint [2] 335345 0
Throughout the study (5 years) and for a ten year follow up period. Altogether 15 years.
Secondary outcome [3] 335346 0
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.
Through out the study participants will be followed up to document whether they have developed cancer. In the event of a cancer, relevant documentation will be obtained through their medical records and primary physician.
Timepoint [3] 335346 0
Throughout the study (5 years) and for a ten year follow up period. Altogether 15 years.
Secondary outcome [4] 335347 0
Changes at 2 & 5 years in the titre of frameshift peptide antibodies from commencement of the prescribed treatment. Serum Samples will be obtained from the participants who consent.
Timepoint [4] 335347 0
Samples will be obtained from the participants who consent. Aliquots will be frozen and shipped to the UK for central processing and analysis.

Eligibility
Key inclusion criteria
1. Age over 18.
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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Regular use of a non-steroidal anti-inflammatory agent on a prescription and/or long-term basis. Regular is defined as > 3 doses per week, for more than 3 months in the last 3 years.
2. Previous regular use of aspirin at a daily dose of 150mg or less does not exclude enrolment but duration and quantity need to be documented in detail. More than 3 months use of > 150mg or more per day in the last 3 years is an exclusion
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

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation system
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Internet-based treatment assignment will be determined by a computer-generated pseudo-random code using random permuted blocks of randomly varying size. Trial participants will be allocated to each treatment arm. The distribution will be in groups of 10 in a ratio of 4:3:3 (600, 300 & 100mg).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
26/05/2017
Date of last participant enrolment
Anticipated
Actual
26/03/2019
Date of last data collection
Anticipated
26/03/2035
Actual
Sample size
Target
160
Accrual to date
Final
141
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 8075 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 11028 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [3] 11029 0
Westmead Hospital - Westmead
Recruitment hospital [4] 11030 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [5] 11031 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 16125 0
3050 - Parkville
Recruitment postcode(s) [2] 22821 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 22822 0
2145 - Westmead
Recruitment postcode(s) [4] 22823 0
4029 - Herston
Recruitment postcode(s) [5] 22824 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 296532 0
Government body
Name [1] 296532 0
Cancer Australia
Country [1] 296532 0
Australia
Funding source category [2] 296533 0
Government body
Name [2] 296533 0
Cancer Council NSW
Country [2] 296533 0
Australia
Funding source category [3] 305544 0
Government body
Name [3] 305544 0
Victorian Cancer Agency
Country [3] 305544 0
Australia
Funding source category [4] 312106 0
Government body
Name [4] 312106 0
Cancer Australia
Country [4] 312106 0
Australia
Primary sponsor type
Hospital
Name
Royal Melbourne Hospital
Address
300 Grattan Street
Royal Melbourne Hospital
Parkville Vic 3050
Country
Australia
Secondary sponsor category [1] 295489 0
None
Name [1] 295489 0
Address [1] 295489 0
Country [1] 295489 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297748 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 297748 0
Office for Research
CITY CAMPUS
Level 2 South West
300 Grattan Street
Parkville Victoria 3050
Ethics committee country [1] 297748 0
Australia
Date submitted for ethics approval [1] 297748 0
Approval date [1] 297748 0
27/06/2016
Ethics approval number [1] 297748 0

Summary
Brief summary
This study will focus on finding the right dose of aspirin for cancer prevention in people with a mismatch repair (MMR) gene defect, the underlying cause of Lynch syndrome, also known as HNPCC (Hereditary Non-Polyposis Colon Cancer).

Who is it for?
You may be eligible to join this study if you are aged 18 years or above and have a confirmed hereditary gene defect in one of the mismatch repair genes; MSH2, MLH1, PMS2 or MSH6 manifesting a classic Lynch syndrome phenotype.

Study details
All study participants will take daily aspirin tablets for duration of two years but will be allocated by chance to one of three different doses (100mg, 300 mg or 600mg). Study investigators will not know which dose any participant is given and you will not be aware of the dose that you are taking. We will then measure number of participants that develop cancers over 5 years.

Our previous study CaPP2 showed that 600mg of aspirin was effective at reducing the risk of cancer in people with Lynch Syndrome and in this study (CaPP3) we would like to determine if 100mg and 300mg of aspirin will be as effective as the higher dose. Taking lower doses of aspirin carries lower risk of side effects such as stomach bleeding occurring.
Trial website
www.capp3.org
Trial related presentations / publications
Public notes
Attachments [1] 1730 1730 0 0
/AnzctrAttachments/372988-HREC 2016 040 RMH PICF Version 1 dated 15 March 2017 Clean Approved.pdf (Participant information/consent)

Contacts
Principal investigator
Name 75010 0
Prof Finlay Macrae
Address 75010 0
Level 3 Centre
Colorectal Medicine and Genetics
300 Grattan Street
The Royal Melbourne Hospital 3050
Victoria, Australia
Country 75010 0
Australia
Phone 75010 0
+61 3 93427580
Fax 75010 0
+61 3 93427848
Email 75010 0
[email protected]
Contact person for public queries
Name 75011 0
Mrs Virginia Bird
Address 75011 0
Level 3 Centre
Colorectal Medicine and Genetics
300 Grattan Street
The Royal Melbourne Hospital 3050
Victoria, Australia
Country 75011 0
Australia
Phone 75011 0
+61 3 93428995
Fax 75011 0
+61 3 93427848
Email 75011 0
[email protected]
Contact person for scientific queries
Name 75012 0
Prof Finlay Macrae
Address 75012 0
Level 3 Centre
Colorectal Medicine and Genetics
300 Grattan Street
The Royal Melbourne Hospital 3050
Victoria, Australia
Country 75012 0
Australia
Phone 75012 0
+61 3 93427580
Fax 75012 0
+61 3 93427848
Email 75012 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.