Universal Endometrial Cancer DNA Sequencing for Detection of Lynch Syndrome and Personalized Care

Study Overview
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Brief Summary
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This clinical trial studies universal screening for deoxyribonucleic acid (DNA) mismatch repair deficiency in patients with endometrial cancer, mutations in the genes responsible for Lynch syndrome (inherited forms of endometrial cancers) and other DNA changes that could help guide treatment strategies. Universal tumor DNA sequencing may help doctors better understand how to personalize care, increase length of life, and increase quality of life in patients with endometrial cancer and their relatives.

Detailed Description
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PRIMARY OBJECTIVES: I. Molecular classification of tumor abnormalities through innovative upfront next-generation DNA sequencing. II. Identify endometrial cancer (EC) patients with inherited EC, specifically Lynch syndrome (LS), using both tumor and normal (blood) DNA testing. III. Develop a comprehensive approach to genetic risk assessment and management including improved cascade testing in at-risk relatives. IV. Provide local access to genetic counseling for patients with harmful germline mutations. V. Identify molecular signatures that may be associated with favorable response to specific treatments (including chemotherapeutic agents, non-surgical options, and novel clinical trials [in particular, patients with mismatch repair (MMR)-deficient or POLE-mutant tumors]). VI. Determine if recurrence likelihood can be predicted from molecular signature. VII. Identify EC patients with select molecular signatures for recruitment to long-term follow-up, cancer prevention, and treatment studies. OUTLINE: Patients with endometrial cancer undergo clinical testing for inherited cancer mutations using blood DNA and via next-generation sequencing of tumor samples. Patients testing positive for Lynch syndrome or other cancer susceptibilities will undergo genetic counseling and testing and counseling will be offered to their family members.

Official Title
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Ohio Prevention and Treatment of Endometrial Cancer (OPTEC) Initiative: Universal Screening for DNA Mismatch Repair Deficiency and Personalized Cancer Treatment

Conditions
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Endometrial Adenocarcinoma, Endometrial Carcinoma, Lynch Syndrome, Relatives

Intervention / Treatment
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* Other: Genetic Counseling
* Other: Genetic Testing
* Other: Laboratory Biomarker Analysis
* Procedure: Mutation Carrier Screening


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult women who had a hysterectomy or diagnostic biopsy proving endometrial adenocarcinoma (any stage) between 10/1/2017 and 4/30/2020, and received care at one of the participating hospitals Adult relatives of the EC patients found to have LS Exclusion Criteria: Individuals must be able to speak and read English; non-English speaking individuals will be excluded Individuals must be able to consent for themselves; those who are unable to consent for themselves for any reason will be excluded Prisoners will be specifically excluded from participation in the study Women who have uterine sarcomas are excluded Pregnant women are not eligible for the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Comprehensive LS genetic testing<br>Testing for inherited forms of cancer and tumor sequencing | Other: Genetic Counseling<br>* Undergo genetic counseling<br>Other: Genetic Testing<br>* Undergo genetic testing<br>* Other names: Genetic Test;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Mutation Carrier Screening<br>* Undergo tumor screening via next-generation sequencing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of endometrial cancer patients with Lynch syndrome | Measured by molecular profiling of tumor deoxyribonucleic acid (DNA) via next-generation sequencing. | Up to 3 years | 
| Incidence of tumors with microsatellite instability and/or somatic POLE mutations | Measured by molecular profiling of tumor DNA via next-generation sequencing. | Up to 3 years |