Finding the Best Dose of Aspirin to Prevent Lynch Syndrome Cancers

NCT ID: NCT02497820

Last Updated: 2016-08-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1800 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2027-09-30

Brief 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).

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.

Conditions

Lynch Syndrome I (Site-specific Colonic Cancer)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

100 mg daily aspirin

They will receive one small tablets each day for two years in a blinded fashion

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

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.

300 mg daily aspirin

They will receive two large enteric coated tablets each day for two years in a blinded fashion

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

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.

600 mg daily aspirin

They will receive two large enteric coated tablets each day for two years in a blinded fashion

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

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.

Interventions

Aspirin

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.

Intervention Type: DRUG

Other Intervention Names

acetylsalicylic acid

Eligibility Criteria

Inclusion Criteria

1. Male or female patients ≥ 18 years.

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. Provision of voluntary written informed consent.

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 at a weekly dose of ≥ 15mg.

4. Known aspirin intolerance or hypersensitivity, including aspirin-sensitive asthma.

5. Existing clinically significant liver impairment.

6. Existing renal failure.

7. Confirmed active peptic ulcer disease within the previous three months.

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 breastfeeding.

12. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Rambam Health Care Campus

OTHER

Sponsor Role: collaborator

Rabin Medical Center

OTHER

Sponsor Role: collaborator

Soroka University Medical Center

OTHER

Sponsor Role: collaborator

Sheba Medical Center

OTHER_GOV

Sponsor Role: collaborator

Tel-Aviv Sourasky Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nadir Arber, MD, MSc, MHA

Role: PRINCIPAL_INVESTIGATOR

Tel-Aviv Sourasky Medical Center

Locations

Sourasky Medical Center

Tel Aviv, , Israel

Countries

Israel

Central Contacts

Maayan Jean, .M.Sc

Role: CONTACT

md0905@gmail.com

0524496437

Michal Shenhaut, DVM

Role: CONTACT

Michalshe@tlvmc.org.il

0584269698

Other Identifiers

0246-14-TLV

Identifier Type: -

Identifier Source: org_study_id