Lynch Syndrome I (Site-specific Colonic Cancer)Phase 3CaPP3 IsraelNCT02497820
Finding the Best Dose of Aspirin to Prevent Lynch Syndrome Cancers
A Phase 3 study testing Aspirin in people with Lynch Syndrome I (Site-specific Colonic Cancer), run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Lynch Syndrome I (Site-specific Colonic Cancer)
- What is being tested?
- Aspirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,800 participants
- Where
- 1 siteIsrael
- Study dates
- Sep 2016to Sep 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female patients ≥ 18 years.
- 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.
- Able to swallow tablets.
- Provision of voluntary written informed consent.
Who cannot join
- 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.
- 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.
- Current methotrexate use at a weekly dose of ≥ 15mg.
- Known aspirin intolerance or hypersensitivity, including aspirin-sensitive asthma.
- Existing clinically significant liver impairment.
- Existing renal failure.
Show all 13Show fewer
- Confirmed active peptic ulcer disease within the previous three months.
- Known bleeding diathesis or concomitant warfarin therapy.
- Inability to comply with study procedures and agents.
- Women reporting that they are pregnant or actively planning to achieve a pregnancy within the next two years.
- Women who are breastfeeding.
- Any significant medical illness that would interfere with study participation.
- Previous use of aspirin for medicinal purposes does not exclude enrolment but duration and quantity need to be documented in detail
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official 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
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).
Read the detailed description
Study design: A randomised, double-blind, dose non-inferiority study.
Study Intervention: Enteric-coated aspirin 100mg, 300mg or 600mg blinded dose daily followed by daily 100mg open label dose daily.
Primary objective: To determine whether the cancer preventive properties of enteric coated aspirin in Lynch syndrome are dose sensitive by comparing overall cumulative Lynch syndrome cancer incidence rates after 5 years in people who took 100mg, 300mg or 600mg enteric coated aspirin for at least 2 years.
Secondary objectives: Compare overall cumulative incidence of primary colorectal cancers using Poisson regression to allow for multiple primaries in individual patients in the three treatment groups.
Compare overall cumulative incidence of primary endometrial cancers using Poisson regression to allow for multiple primaries in individual patients in the three treatment groups.
Compare overall cumulative incidence of cancers of all types, using Poisson regression to allow for multiple primaries in individual patients in the three treatment groups.
The burden of adverse events associated with the different aspirin doses in this relatively young and healthy population will be documented.
Primary outcome: 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.
Number of study sites: 4 ISRAEL sites. 20 sites all over the world.
Study population/size: 300 patients in ISRAEL. UK 1000-1500 patients. Total with International 3,000 patients.
Study duration: 7 years.
- Being tested
- Aspirin
- Medical subject headings
- Lynch syndrome I (site-specific colonic cancer)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
Also called acetylsalicylic acid
Aspirin (acetylsalicylic acid) has a marketing approval for use in the EU and is widely available as an over the counter medicine. However it is not being used within its licensed indication and the aspirin (at any dose in this study) will be treated as an investigational medicinal product (IMP).
Tablets will be provided as enteric-coated 100mg or 300mg tablets for oral use. All patients will receive at least some dose of aspirin but blinding to the actual dose will be achieved by the use of 'dummy' tablets using the same excipients as in the active formulation of the aspirin minus the active ingredient.
The aspirin and dummy tablets should be stored at room temperature below 25⁰C in a dry place.
| Study group | Role | What they receive |
|---|---|---|
| 100 mg daily aspirin | Active comparator | They will receive one small tablets each day for two years in a blinded fashion Receives: Drug: Aspirin |
| 300 mg daily aspirin | Active comparator | They will receive two large enteric coated tablets each day for two years in a blinded fashion Receives: Drug: Aspirin |
| 600 mg daily aspirin | Active comparator | They will receive two large enteric coated tablets each day for two years in a blinded fashion Receives: Drug: Aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
cancer preventive properties of enteric coated aspirin in Lynch syndrome are dose sensitive by comparing overall cumulative Lynch syndrome cancer
The number of new primary mismatch repair deficient cancers ("Lynch syndrome cancers") at 5 years which develop in participants who remain on prescribed treatment for a minimum of 2 years.
Measured: 5 years
Secondary outcomes (5)
Overall cumulative of new colorectal cancers incidence rates after 5 years
The number of new colorectal cancers at 5 years which develop in participants who remain on prescribed treatment for a minimum of 2 years.
Measured: 5 years
Overall cumulative of new endometrial cancers incidence rates after 5 years
The number of new endometrial cancers at 5 years which develop in participants who remain on prescribed treatment for a minimum of 2 years.
Measured: 5 years
Overall cumulative of new new cancers of all types incidence rates after 5 years
- The number of new cancers of all types at 5 years which develop in participants who remain on prescribed treatment for a minimum of 2 years.
Measured: 5 years
Overall cumulative of changes in the titre of frameshift peptide antibodies after 2 & 5 years
Changes at 2 \& 5 years in the titre of frameshift peptide antibodies from commencement of the prescribed treatment.
Measured: 5 years
Overall cumulative of of new adenomas at five years
The number of new adenomas at five years
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2015 (estimated)
- Study startSep 2016
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lynch Syndrome I (Site-specific Colonic Cancer)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 1,800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tel-Aviv Sourasky Medical Center
- Sponsor type
- Other government
- Collaborators
- Rambam Health Care Campus, Rabin Medical Center, Soroka University Medical Center, Sheba Medical Center
- Responsible party
- Sponsor
- Investigators
- Nadir Arber, MD, MSc, MHA, Principal investigator, Tel-Aviv Sourasky Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02497820
- Sponsor's protocol ID
- 0246-14-TLV
- Acronym
- CaPP3 Israel
- Status last verified
- Aug 2016
- First submitted
- 7 Jul 2015
- Last updated
- 25 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Burn J, Borthwick GM, Elliott F, Macrae F, Ong KR, Kraus AC, Arber N, Mecklin JP, Alonso A, Woodward ER, Evans DG, Murray A, Snape K, Cleaver RE, Shaw A, Thomas HJW, Kumar AV, Halliday D, Side LE, Harrison RE, Davidson R, Armstrong R, Cook J, Hart R, Morrison PJ, Barwell JG, Donaldson A, Kemp Z, Murray J, Miedzybrodzka Z, Pottinger C, Berg J, Gallon R, Bishop DT; CaPP3 co-investigators. Aspirin for cancer prevention in individuals with Lynch syndrome: first results from the CaPP3 multicentre, randomised, double-blind, non-inferiority trial. Lancet Gastroenterol Hepatol. 2026 Sep;11(9):760-774. doi: 10.1016/S2468-1253(26)00114-7. Epub 2026 Jul 9.
PubMed 42425127
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02497820
- Acronym / sponsor ID
- CaPP3 Israel / 0246-14-TLV
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,800 participants (estimated)
- Lead sponsor
- Tel-Aviv Sourasky Medical CenterOther government
- Collaborators
- Rambam Health Care Campus, Rabin Medical Center, Soroka University Medical Center, Sheba Medical Center
- Study start
- Sep 2016
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 15 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Study design: A randomised, double-blind, dose non-inferiority study.
Study Intervention: Enteric-coated aspirin 100mg, 300mg or 600mg blinded dose daily followed by daily 100mg open label dose daily.
Primary objective: To determine whether the cancer preventive properties of enteric coated aspirin in Lynch syndrome are dose sensitive by comparing overall cumulative Lynch syndrome cancer incidence rates after 5 years in people who took 100mg, 300mg or 600mg enteric coated aspirin for at least 2 years.
Secondary objectives: Compare overall cumulative incidence of primary colorectal cancers using Poisson regression to allow for multiple primaries in individual patients in the three treatment groups.
Compare overall cumulative incidence of primary endometrial cancers using Poisson regression to allow for multiple primaries in individual patients in the three treatment groups.
Compare overall cumulative incidence of cancers of all types, using Poisson regression to allow for multiple primaries in individual patients in the three treatment groups.
The burden of adverse events associated with the different aspirin doses in this relatively young and healthy population will be documented.
Primary outcome: 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.
Number of study sites: 4 ISRAEL sites. 20 sites all over the world.
Study population/size: 300 patients in ISRAEL. UK 1000-1500 patients. Total with International 3,000 patients.
Study duration: 7 years.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 100 mg daily aspirin | Active comparator | Drug: AspirinThey will receive one small tablets each day for two years in a blinded fashion |
| 300 mg daily aspirin | Active comparator | Drug: AspirinThey will receive two large enteric coated tablets each day for two years in a blinded fashion |
| 600 mg daily aspirin | Active comparator | Drug: AspirinThey will receive two large enteric coated tablets each day for two years in a blinded fashion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female patients ≥ 18 years.
- 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.
- Able to swallow tablets.
- Provision of voluntary written informed consent.
Key exclusion criteria (13 listed)
- 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.
- 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.
- Current methotrexate use at a weekly dose of ≥ 15mg.
- Known aspirin intolerance or hypersensitivity, including aspirin-sensitive asthma.
- Existing clinically significant liver impairment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AspirinAlso: acetylsalicylic acidAspirin (acetylsalicylic acid) has a marketing approval for use in the EU and is widely available as an over the counter medicine. However it is not being used within its licensed indication and the aspirin (at any dose in this study) will be treated as an investigational medicinal product (IMP). Tablets will be provided as enteric-coated 100mg or 300mg tablets for oral use. All patients will receive at least some dose of aspirin but blinding to the actual dose will be achieved by the use of 'dummy' tablets using the same excipients as in the active formulation of the aspirin minus the active ingredient. The aspirin and dummy tablets should be stored at room temperature below 25⁰C in a dry place. | Drug | 100 mg daily aspirin, 300 mg daily aspirin, 600 mg daily aspirin |
Primary outcome
cancer preventive properties of enteric coated aspirin in Lynch syndrome are dose sensitive by comparing overall cumulative Lynch syndrome cancer
Time frame: 5 years
The number of new primary mismatch repair deficient cancers ("Lynch syndrome cancers") at 5 years which develop in participants who remain on prescribed treatment for a minimum of 2 years.
5 secondary outcomes
Overall cumulative of new colorectal cancers incidence rates after 5 years
Time frame: 5 years
Overall cumulative of new endometrial cancers incidence rates after 5 years
Time frame: 5 years
Overall cumulative of new new cancers of all types incidence rates after 5 years
Time frame: 5 years
Overall cumulative of changes in the titre of frameshift peptide antibodies after 2 & 5 years
Time frame: 5 years
Overall cumulative of of new adenomas at five years
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2016.
- Derived from this study: PubMed 42425127Burn J, Borthwick GM, Elliott F, Macrae F, Ong KR, Kraus AC, Arber N, Mecklin JP, Alonso A, Woodward ER, Evans DG, Murray A, Snape K, Cleaver RE, Shaw A, Thomas HJW, Kumar AV, Halliday D, Side LE, Harrison RE, Davidson R, Armstrong R, Cook J, Hart R, Morrison PJ, Barwell JG, Donaldson A, Kemp Z, Murray J, Miedzybrodzka Z, Pottinger C, Berg J, Gallon R, Bishop DT; CaPP3 co-investigators. Aspirin for cancer prevention in individuals with Lynch syndrome: first results from the CaPP3 multicentre, randomised, double-blind, non-inferiority trial. Lancet Gastroenterol Hepatol. 2026 Sep;11(9):760-774. doi: 10.1016/S2468-1253(26)00114-7. Epub 2026 Jul 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nadir Arber, MD, MSc, MHA principal investigator
Tel-Aviv Sourasky Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Aspirin in people with Lynch Syndrome I (Site-specific Colonic Cancer), run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 25 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maayan Jean, .M.Sc (0524496437, md0905@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cancer preventive properties of enteric coated aspirin in Lynch syndrome are dose sensitive by comparing overall cumulative Lynch syndrome cancer (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02497820, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2016.