Screening Method for Lynch Syndrome in Endometrial and Ovarian Cancer

(LS2 Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Uterine adenosarcoma, Leiomyosarcoma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

886 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks better methods to identify women with Lynch Syndrome, a genetic condition that raises cancer risk, particularly in those with endometrial or ovarian cancer. The study employs an enhanced screening strategy and provides genetic counseling to detect the syndrome. Women diagnosed with endometrial cancer within the last six months, who are willing to participate, might be suitable candidates. If Lynch Syndrome is detected, their close family members can also join and undergo testing. The trial aims to improve early detection, guide treatment, and evaluate the long-term benefits of this approach. As an unphased trial, it offers participants a unique chance to contribute to groundbreaking research that could enhance detection and prevention strategies for Lynch Syndrome.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this enhanced screening strategy is safe for identifying Lynch Syndrome?

Research shows that a new screening method for Lynch Syndrome effectively identifies individuals at risk for this genetic condition. This screening detects specific genetic changes linked to Lynch Syndrome, which significantly increase the risk of cancers such as colorectal and endometrial cancer. The screening is non-invasive, meaning it doesn't involve surgery or entering the body, and is generally safe. Its primary purpose is to identify individuals who might benefit from further genetic counseling and testing.

Genetic counseling is a common practice for those at risk of inherited conditions like Lynch Syndrome. It involves discussing personal and family medical history to assess the likelihood of a genetic condition. This process is safe and consists only of conversation and advice.

Overall, both the new screening method and genetic counseling are safe for participants. They aim to help identify and manage cancer risks, rather than serving as treatments with direct side effects. The main goal is to provide information that can lead to early detection and prevention strategies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to enhance the screening process for Lynch Syndrome in individuals with endometrial and ovarian cancer. Unlike standard screening methods, which might not fully capture all at-risk individuals, this enhanced screening strategy offers a more comprehensive approach, potentially leading to earlier and more accurate detection of Lynch Syndrome. Additionally, incorporating genetic counseling helps participants understand their risks and options better, empowering them with knowledge and support. This trial could pave the way for more personalized and effective care, improving outcomes for those with or at risk of these cancers.

What evidence suggests that this enhanced screening strategy is effective for identifying Lynch Syndrome?

Research has shown that improved screening methods effectively detect Lynch Syndrome in women, significantly increasing the risk of endometrial and ovarian cancers. This trial will evaluate an Enhanced Screening Strategy to identify those at risk, enabling earlier intervention. Early detection through these screenings improves prevention and management of these cancers.

Genetic counseling, another component of this trial, plays a crucial role. It helps individuals understand their risk and make informed decisions about genetic testing. Studies indicate that genetic counseling increases the rate of genetic testing in families, supporting early detection and prevention strategies for cancers related to Lynch Syndrome. ^{2 3 6 7 8}

Who Is on the Research Team?

Sarah Ferguson, MD

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

This trial is for women aged 18-70 in Canada with endometrial cancer (excluding certain types) diagnosed within the last 6 months. Participants must have tumor tissue available and be able to consent. Their adult first-degree relatives can join if they give consent and live in Canada.

Inclusion Criteria

I was diagnosed with cancer less than 6 months ago.

First-degree Relatives must be willing and able to give informed consent for participation in the study

First-degree Relatives must reside in Canada

Exclusion Criteria

First-degree Relatives must not reside outside of Canada

My cancer is not uterine adenosarcoma, leiomyosarcoma, or endometrial stromal sarcoma.

My ovarian cancer is not purely serous or mucinous.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Genetic Counselling and Testing

Participants at risk for Lynch Syndrome are referred to genetic counselling and undergo genetic testing

4-6 weeks

2 visits (in-person)

Follow-up

Participants found to have Lynch Syndrome are monitored for adherence to screening guidelines and risk-reducing strategies

10 years

Annual updates (virtual or in-person)

Research and Sequencing Studies

Consenting participants provide blood and tumor tissue samples for sequencing studies to investigate genetic basis for Lynch Syndrome

3-5 years

What Are the Treatments Tested in This Trial?

Interventions

• Educational Material
• Enhanced Screening Strategy
• Genetic Counselling
• Questionnaire

Trial Overview The study tests an enhanced screening strategy for Lynch Syndrome among women with specific cancers, offering genetic counseling and testing. It also evaluates adherence to recommended guidelines over ten years after a Lynch Syndrome diagnosis.

How Is the Trial Designed?

Group I: Endometrial and Ovarian Cancer Participants Experimental Treatment 1 Intervention

All study subjects will be offered the same options for screening and follow-up.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Mount Sinai Hospital, Canada

Collaborator

Trials

210

Recruited

70,700+

Sunnybrook Health Sciences Centre

Collaborator

Trials

693

Recruited

1,569,000+

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

Toronto Metropolitan University

Collaborator

Trials

95

Recruited

19,300+

Ryerson University

Collaborator

Trials

77

Recruited

7,800+

Hamilton Health Sciences Corporation

Collaborator

Trials

380

Recruited

345,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11733057/

Outcomes of endometrial cancer prevention strategies in ... We therefore described gynaecological surveillance and surgery outcomes in a nation-wide Lynch syndrome cohort.

2. uptodate.com uptodate.com/contents/lynch-syndrome-hereditary-nonpolyposis-colorectal-cancer-screening-and-prevention-of-endometrial-and-ovarian-cancer/abstract/46

Screening and prevention of endometrial and ovarian cancer BACKGROUND Women with Lynch syndrome (hereditary nonpolyposis colorectal cancer) have an increased lifetime risk for endometrial and ovarian cancer.

3. sciencedirect.com sciencedirect.com/science/article/pii/S154235652500326X

Cost-effectiveness of Lynch Syndrome Screening in ... Testing all colorectal cancers (CRCs) for mismatch repair status to evaluate for Lynch syndrome (LS) has been recommended for years.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02494791?term=serous&cond=endometrial%20cancer&viewType=Table&checkSpell=&rank=8

Universal Screening for Lynch Syndrome in Women With ... This study will maximize identification of women with Lynch Syndrome using an enhanced screening strategy to identify those at risk.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa043146

Screening for the Lynch Syndrome (Hereditary ... Routine molecular screening of patients with colorectal adenocarcinoma for the Lynch syndrome identified mutations in patients and their family members.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK431096/

Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) Identifying patients with Lynch syndrome is important because these patients have up to an 80% lifetime risk of colorectal cancer, a 60% ...

7. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00585-6/fulltext

Outcomes of endometrial cancer prevention strategies in ... Systematic review of the impact of registration and screening on colorectal cancer incidence and mortality in familial adenomatous polyposis and Lynch syndrome.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24009861

Screening and risk reducing surgery for endometrial or ... There is limited evidence to support screening for endometrial and ovarian cancer in Lynch syndrome and data on mortality reduction are not available.