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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lynch Syndrome; Relatives; Endometrial Carcinoma; Endometrial Adenocarcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Genetic Counseling; Other: Genetic Testing; Procedure: Mutation Carrier Screening

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1002
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Akron City Hospital/Cooper Cancer Center
    • Canton, Ohio, United States, 44710
      • Aultman Health Foundation
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cincinnati, Ohio, United States, 45245
      • TriHealth Cancer Institute-Westside
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43214
      • Ohio Health
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Toledo, Ohio, United States, 43608
      • Mercy Health - St. Vincent Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Investigators: Principal Investigator: Paul Goodfellow, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2018
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: March 1, 2018
• First Submitted That Met QC Criteria: March 7, 2018
• First Posted (Actual): March 9, 2018

Study Record Updates

• Last Update Posted (Estimate): December 6, 2022
• Last Update Submitted That Met QC Criteria: December 2, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; 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; Endometrial Neoplasms
• Other Study ID Numbers: OSU-17149; NCI-2018-00218 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No