Universal Screening for Lynch Syndrome in Women With Endometrial and Non-Serous Ovarian Cancer (LS2)

May 16, 2022 updated by: University Health Network, Toronto
This study will maximize identification of women with Lynch Syndrome using an enhanced screening strategy to identify those at risk. These women will be referred to genetic counselling for testing and those found to have Lynch Syndrome will be asked to invite first degree relatives to participate and undergo genetic testing for Lynch Syndrome. Screening guidelines and risk reducing surgery options for participants found to have Lynch Syndrome will be reinforced by the study and adherence to these guidelines will be assessed annually for ten years following Lynch Syndrome diagnosis to assess the impact and cost-effectiveness of this enhanced screening approach.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Lynch Syndrome increases an individual's risk for several cancers, such as colorectal, endometrial (EC) and certain types of ovarian cancer (OC). Lynch Syndrome is caused by inherited changes in mismatch repair (MMR) genes. In this study we will establish the proportion of EC and OC patients with Lynch Syndrome. We will screen all EC and OC patients by performing MMR immunohistochemistry (IHC) on their surgical specimen. These data will then be used along with family history data to determine which women are at high risk of Lynch Syndrome. We will facilitate the referral of all women at risk for Lynch Syndrome to genetic counselling on behalf of their treating physician. First degree relatives of those patients found to have Lynch Syndrome who consent to participate in the study will also be referred to genetics by the study PI. We will encourage all participants found to have Lynch Syndrome to attend regular colonoscopy screening to prevent colorectal cancer, and (for females with Lynch Syndrome) consideration of gynecologic risk reducing surgery to prevent endometrial and ovarian cancers. We will assess adherence to Lynch Syndrome screening guidelines in this population and will determine if our universal screening strategy is feasible and cost-effective for widespread implementation across Canada in an effort to prevent Lynch Syndrome associated cancers in women and their families. In addition to this, consenting patients may provide blood and tumour tissue samples for sequencing studies which will investigate the genetic basis for Lynch Syndrome and shed light on cases of MMR loss in the absence of germline mutation.

Study Type

Interventional

Enrollment (Actual)

886

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5T 2M9
        • University Health Network - Princess Margaret Hospital

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 to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria (Patients):

  • 18-70 years old
  • endometrial cancer (all grades, stages and histologic subtypes except stromal sarcoma, carcinosarcoma)
  • cancer diagnosed within 6 months of consent
  • tumour tissue available for MMR IHC
  • willing and able to give informed consent for participation in study

Exclusion Criteria (Patients):

  • patients under 18 years old or over 70 years old
  • patients with uterine adenosarcoma, leiomyosarcoma or endometrial stromal sarcoma
  • patients with pure serous or pure mucinous ovarian carcinoma
  • patients unwilling or unable to participate in the informed consent process

Inclusion Criteria (First-degree Relatives)

  • minimum 18 years old
  • reside in Canada
  • willing and able to give informed consent for participation in study

Exclusion Criteria (First-degree Relatives):

  • under 18 years old
  • reside outside of Canada
  • unwilling or unable to participate in the informed consent process

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: Screening
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Endometrial and Ovarian Cancer Participants
All study subjects will be offered the same options for screening and follow-up.
Behavioral: Questionnaire, Educational Material
Participants in this study will be given educational material about Lynch Syndrome and genetic testing for this condition. They will be asked to complete questionnaires about their family cancer history, personal health history and attitudes toward genetic testing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adherence to screening guidelines (colonoscopy and gynecologic risk-reducing surgery) in participants found to have Lynch Syndrome
Time Frame: short-term assessment at 1 year after diagnosis, long-term assessment for up to 10 years after diagnosis
Participants found to have Lynch Syndrome will be followed after diagnosis and asked to update the study annually with information about any colorectal cancer screening (colonoscopy) and/or gynecologic risk-reducing surgery they've undergone. This information will be used to assess the success of the enhanced universal screening protocol in helping treat pre-cancerous lesions and therefore prevent a possible cancer as well as aid in detection of early malignancies that otherwise may have gone undetected.
short-term assessment at 1 year after diagnosis, long-term assessment for up to 10 years after diagnosis
Cost-effectiveness of universal enhanced screening strategy to identify women with Lynch Syndrome and their family members via cascade testing
Time Frame: short-term assessment at 1 year after diagnosis, long-term assessment for up to 10 years after diagnosis
Data about adherence to screening guidelines and the outcome of screening procedures will be used to inform cost-effectiveness models assessing the feasibility of implementing this enhanced universal screening strategy for Lynch Syndrome in institutions across Canada.
short-term assessment at 1 year after diagnosis, long-term assessment for up to 10 years after diagnosis

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Lynch Syndrome in an unselected group of women with endometrial and non-serous ovarian cancer
Time Frame: 3 years
This study will add data about the number of Lynch Syndrome cases among a large cohort of endometrial cancer patients in Canada, adding to previous work. This will be the first prospective study to assess Lynch Syndrome incidence in non-serous, non-mucinous ovarian cancer patients in Canada.
3 years
Discovery of novel genetic mutations and molecular events in unexplained MMR loss (Lynch-like Syndrome)
Time Frame: 3-5 years
This study will investigate tumour samples from women with unexplained MMR loss (MMR IHC deficient without a germline mutation) to probe what other factors may contribute to Lynch-like Syndrome. Currently these patients are believed to have an intermediate risk for Lynch-associated cancers and are counselled accordingly. Further investigation into the biology of this condition may yield more effective strategies for stratifying and managing risk for Lynch-like Syndrome patients.
3-5 years

Collaborators and Investigators

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

Sponsor

University Health Network, Toronto

Collaborators

Sunnybrook Health Sciences Centre
University of Toronto
Hamilton Health Sciences Corporation
Ryerson University
Mount Sinai Hospital, Canada

Investigators

  • Principal Investigator: Sarah Ferguson, MD, Princess Margaret Cancer Centre

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 (Actual)

July 1, 2015

Primary Completion (Actual)

July 1, 2020

Study Completion (Anticipated)

July 1, 2025

Study Registration Dates

First Submitted

July 7, 2015

First Submitted That Met QC Criteria

July 7, 2015

First Posted (Estimate)

July 10, 2015

Study Record Updates

Last Update Posted (Actual)

May 17, 2022

Last Update Submitted That Met QC Criteria

May 16, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14-8533CE

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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