- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02497820
Finding the Best Dose of Aspirin to Prevent Lynch Syndrome Cancers (CaPP3 Israel)
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
Study Overview
Status
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
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Maayan Jean, .M.Sc
- Phone Number: 0524496437
- Email: md0905@gmail.com
Study Contact Backup
- Name: Michal Shenhaut, DVM
- Phone Number: 0584269698
- Email: Michalshe@tlvmc.org.il
Study Locations
-
-
-
Tel Aviv, Israel, 64239
- Sourasky Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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
Study Plan
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:
|
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:
|
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:
|
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
Sponsor
Collaborators
Investigators
- Principal Investigator: Nadir Arber, MD, MSc, MHA, Tel-Aviv Sourasky Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Metabolic Diseases
- Neoplasms
- Neoplasms by Site
- Disease
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Genetic Diseases, Inborn
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Colorectal Neoplasms
- Neoplastic Syndromes, Hereditary
- DNA Repair-Deficiency Disorders
- Syndrome
- Colorectal Neoplasms, Hereditary Nonpolyposis
- Colonic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Platelet Aggregation Inhibitors
- Cyclooxygenase Inhibitors
- Antipyretics
- Aspirin
Other Study ID Numbers
- 0246-14-TLV
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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