Early Detection of Endometrial/Ovarian Cancer and Hereditary Predisposition of These Cancers (FemGene)

Phase III Diagnostic Trial for Early Detection of Endometrial/Ovarian Cancer and Hereditary Predisposition of These Cancers

Early stage high-grade cancer, endometrial and ovarian, has few, if any, symptoms or signs. When symptoms appear, the disease is commonly in advanced stage meaning it has left the gynaecological organs and metastasized to the pelvic/abdominal cavity. The McGill research group had showed in the DOvEE trial (NCT02296307), that fast-track assessment with transvaginal ultrasound scans (TVUS) and serial CA125 of women with vague symptoms associated with ovarian and endometrial cancer did diagnose these cancers earlier in the disease trajectory, with low-volume resectable disease, but only after the cancer had already become Stage III. One way to detect these cancers earlier is to screen asymptomatic women. Unfortunately, none of the currently available tests, including TVUS and CA-125 have been shown to be useful for screening for ovarian or endometrial cancer.

The McGill team has developed a genomic assay to screen and detect these cancers earlier in the trajectory than is currently the case. The test identifies pathogenic somatic mutations (necessary early steps in the development of these cancers), in an uterine cytological sample. It is able to do so by incorporating a machine-learning derived classifier that can discriminate the mutational signature of these cancers from benign disease with a sensitivity of 80% and a specificity of 100% in a healthy population of peri- and post-menopausal women. In addition to the uterine sample, the test includes a saliva sample that acts as an internal control but can also identify germline pathogenic variants that predispose to hereditary endometrial/ovarian cancers as well as breast, pancreas, and colon cancers.

The test was developed in a retrospective population in whom the assay was done pre-operatively and the diagnosis of malignancy versus benign gynecological disease was confirmed by detailed pathological analysis of the uterus, tubes, and ovaries after surgical resection (NCT02288676). The test is now ready to be tested as a phase III diagnostic test in the general population to see if these results are just as promising in the community at large.

Study Overview

• Status: Recruiting
• Conditions: Diagnoses Disease
• Intervention / Treatment: Diagnostic test: DOvEEgene test

• Study Type: Interventional
• Enrollment (Estimated): 5600
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lucy Gilbert, MD; Phone Number: 34049 514-934-1934; Email: gyne-oncologysec@mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • McGill University Health Centre, Royal Victoria Hospital
      • Contact: Lucy Gilbert, MD,MSc,FRCOG; Phone Number: 34049 514-934-1934; Email: lucy.gilbert@mcgill.ca
      • Contact: Claudia Martins, MD, PhD; Phone Number: 36794 514-934-1934; Email: claudia.martins@mcgill.ca
      • Principal Investigator: Lucy Gilbert, MD,MSc,FRCOG
    • Montréal, Quebec, Canada, H4A 3K6
      • Recruiting
      • Queen Elizabeth Health Complex
      • Contact: Lucy Gilbert, MD; Phone Number: 34049 514-934-1934; Email: gyne-oncologysec@mcgill.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

- Capacity to understand study and provide informed consent

Exclusion Criteria:

• Prior hysterectomy
• Be pregnant
• Be nursing
• Be undergoing any fertility treatment
• Have had recent history of uterine perforation

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early diagnosis of ovarian and endometrial cancers	Through the identification of pathogenic somatic mutations in uterine pap sample in combination with an established machine learning algorithm, the team will discriminate cancer from benign disease in participant samples.	3 years
Identification of germline mutations	To determine the proportion of the study population who are carriers of clinically significant pathogenic germline mutations.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate women's experience related to study procedures	Assess women's experience to the genomic uterine pap sampling process using an acceptability questionnaire. It is important the participant has a good experience with the sampling and healthcare professional.	3 years
Evaluate effects on quality of life from study participation	We will assess effects on quality of life (QoL) to study participants, such as anxiety while awaiting results, interventions for false positives results and etc. via the SF-36 questionnaire.	3 years
Evaluate costs of unnecessary intervention	We will track the cost of every intervention resulting from a positive test, till we determine whether it was a false positive or not. For instances of a false positive result, we will consider the associated costs via a health economics analysis.	3 years

Collaborators and Investigators

• Sponsor: McGill University
• Collaborators: McGill University Health Centre/Research Institute of the McGill University Health Centre; Research Institute of the McGill University Health Center; Genome Canada; Genome Quebec

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2021
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: May 7, 2021
• First Submitted That Met QC Criteria: May 12, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Actual): June 17, 2025
• Last Update Submitted That Met QC Criteria: June 13, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Screening; Ovarian Cancer; Genomics; Endometrial Cancer; Early detection
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Neoplasms by Histologic Type; Genital Diseases, Female; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Disease Susceptibility
• Other Study ID Numbers: 2020-6430

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