Finding the Best Dose of Aspirin to Prevent Lynch Syndrome Cancers (CaPP3 Israel)

August 24, 2016 updated by: Tel-Aviv Sourasky Medical Center

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).

Study Overview

Status

Not yet recruiting

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

1800

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Tel Aviv, Israel, 64239
        • Sourasky Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 100 mg daily aspirin
They will receive one small tablets each day for two years in a blinded fashion

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.

Other Names:
  • acetylsalicylic acid
Active Comparator: 300 mg daily aspirin
They will receive two large enteric coated tablets each day for two years in a blinded fashion

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.

Other Names:
  • acetylsalicylic acid
Active Comparator: 600 mg daily aspirin
They will receive two large enteric coated tablets each day for two years in a blinded fashion

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.

Other Names:
  • acetylsalicylic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall cumulative of new colorectal cancers incidence rates after 5 years
Time Frame: 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.
5 years
Overall cumulative of new endometrial cancers incidence rates after 5 years
Time Frame: 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.
5 years
Overall cumulative of new new cancers of all types incidence rates after 5 years
Time Frame: 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.
5 years
Overall cumulative of changes in the titre of frameshift peptide antibodies after 2 & 5 years
Time Frame: 5 years
Changes at 2 & 5 years in the titre of frameshift peptide antibodies from commencement of the prescribed treatment.
5 years
Overall cumulative of of new adenomas at five years
Time Frame: 5 years
The number of new adenomas at five years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Nadir Arber, MD, MSc, MHA, Tel-Aviv Sourasky Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2016

Primary Completion (Anticipated)

September 1, 2027

Study Completion (Anticipated)

September 1, 2027

Study Registration Dates

First Submitted

July 7, 2015

First Submitted That Met QC Criteria

July 14, 2015

First Posted (Estimate)

July 15, 2015

Study Record Updates

Last Update Posted (Estimate)

August 25, 2016

Last Update Submitted That Met QC Criteria

August 24, 2016

Last Verified

August 1, 2016

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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