Finding the Best Dose of Aspirin to Prevent Lynch Syndrome Cancers

NCT02497820 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 0246-14-TLV
• Study Type: interventional
• Target: 1,800
• Locations: 1 country
• Sites: 1

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).

Conditions

Lynch Syndrome I (Site-specific Colonic Cancer)

Outcome Measures

Primary Outcomes (1)

• 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.

  5 years

Secondary Outcomes (5)

• Overall cumulative of new colorectal cancers incidence rates after 5 years

  5 years

• Overall cumulative of new endometrial cancers incidence rates after 5 years

  5 years

• Overall cumulative of new new cancers of all types incidence rates after 5 years

  5 years

• Overall cumulative of changes in the titre of frameshift peptide antibodies after 2 & 5 years

  5 years

• Overall cumulative of of new adenomas at five years

  5 years

Study Arms (3)

100 mg daily aspirin

ACTIVE COMPARATOR

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

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

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

Drug: Aspirin

Interventions

Aspirin 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.

Also known as: acetylsalicylic acid

100 mg daily aspirin; 300 mg daily aspirin; 600 mg daily aspirin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Tel-Aviv Sourasky Medical Center: lead
• Rambam Health Care Campus: collaborator
• Rabin Medical Center: collaborator
• Soroka University Medical Center: collaborator
• Sheba Medical Center: collaborator

Study Sites (1)

Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

MeSH Terms

Conditions

Lynch syndrome I (site-specific colonic cancer)

Interventions

Aspirin

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Nadir Arber, MD, MSc, MHA

  Tel-Aviv Sourasky Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maayan Jean, .M.Sc

CONTACT

0524496437; md0905@gmail.com

Michal Shenhaut, DVM

CONTACT

0584269698; Michalshe@tlvmc.org.il

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2015
• First Posted: July 15, 2015
• Study Start: September 1, 2016
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: August 25, 2016

Record last verified: 2016-08

Locations

IL (1)