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

Study Overview
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Brief Summary
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Early stage high-grade cancer, endometrial and ovarian, has few, if any, symptoms or signs. When symptoms appear, the disease may be in advanced stage as the disease 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 deep machine-learning derived classifier that can discriminate the mutational signature of these cancers from benign disease with a sensitivity of 70% and a specificity of 100% in a population with high background mutational burden. In addition to the intra-uterine cytological sample, the test includes an assay of a saliva sample to identify germline mutations that predispose to hereditary endometrial/ovarian cancers as well as breast 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.

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

Conditions
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Diagnoses Disease

Intervention / Treatment
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* Diagnostic Test: DOvEEgene test


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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

| Intervention/Treatment |
| --- |
|Diagnostic Test: DOvEEgene test|Women participating in the study will undergo a genomic uterine pap test, DOvEEgene test, for the screening of ovarian and endometrial cancers|

What is the study measuring?
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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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of germline mutations | Detection of pathogenic germline mutations in participants' saliva sample to mitigate risks of other cancers (namely breast, ovarian, uterine and colon cancers) and diseases if participant opts for disclosure of results. | 3 years | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian Cancer, Endometrial Cancer, Genomics, Screening, Early detection