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

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ClinicalTrials.gov Identifier: NCT02497820
Recruitment Status : Not yet recruiting
First Posted : July 15, 2015
Last Update Posted : August 25, 2016
Sponsor:
Collaborators:
Rambam Health Care Campus
Rabin Medical Center
Soroka University Medical Center
Sheba Academic Medical Center Hospital
Information provided by (Responsible Party):
Tel-Aviv Sourasky Medical Center

Tracking Information
First Submitted Date  ICMJE July 7, 2015
First Posted Date  ICMJE July 15, 2015
Last Update Posted Date August 25, 2016
Study Start Date  ICMJE September 2016
Estimated Primary Completion Date September 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 14, 2015)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 14, 2015)
  • 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.
  • 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.
  • 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.
  • 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.
  • Overall cumulative of of new adenomas at five years [ Time Frame: 5 years ]
    The number of new adenomas at five years
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Finding the Best Dose of Aspirin to Prevent Lynch Syndrome Cancers
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Lynch Syndrome I (Site-specific Colonic Cancer)
Intervention  ICMJE Drug: 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.

Other Name: acetylsalicylic acid
Study Arms  ICMJE
  • Active Comparator: 100 mg daily aspirin
    They will receive one small tablets each day for two years in a blinded fashion
    Intervention: Drug: Aspirin
  • Active Comparator: 300 mg daily aspirin
    They will receive two large enteric coated tablets each day for two years in a blinded fashion
    Intervention: Drug: Aspirin
  • Active Comparator: 600 mg daily aspirin
    They will receive two large enteric coated tablets each day for two years in a blinded fashion
    Intervention: Drug: Aspirin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: July 14, 2015)
1800
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2027
Estimated Primary Completion Date September 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Maayan Jean, .M.Sc 0524496437 md0905@gmail.com
Contact: Michal Shenhaut, DVM 0584269698 Michalshe@tlvmc.org.il
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02497820
Other Study ID Numbers  ICMJE 0246-14-TLV
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tel-Aviv Sourasky Medical Center
Study Sponsor  ICMJE Tel-Aviv Sourasky Medical Center
Collaborators  ICMJE
  • Rambam Health Care Campus
  • Rabin Medical Center
  • Soroka University Medical Center
  • Sheba Academic Medical Center Hospital
Investigators  ICMJE
Principal Investigator: Nadir Arber, MD, MSc, MHA Tel-Aviv Sourasky Medical Center
PRS Account Tel-Aviv Sourasky Medical Center
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP