Clinical trial NCT04891029: Early Detection of Endometrial/Ovarian Cancer and Hereditary Predisposition of These Cancers
Official title: Phase III Diagnostic Trial for Early Detection of Endometrial/Ovarian Cancer and Hereditary Predisposition of These Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diagnoses Disease
Keywords: Ovarian Cancer
Endometrial Cancer
Genomics
Screening
Early detection
Lead sponsor: McGill University
Sponsor class: OTHER
Collaborators: name: Genome Canada
name: Genome Quebec
name: Research Institute of the McGill University Health Center
name: McGill University Health Centre/Research Institute of the McGill University Health Centre
First posted: 2021-05-18
Enrollment: 5600
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Early diagnosis of ovarian and endometrial cancers
timeFrame: 3 years
measure: Identification of germline mutations
timeFrame: 3 years
Secondary outcomes:
measure: Evaluate women's experience related to study procedures
timeFrame: 3 years
measure: Evaluate effects on quality of life from study participation
timeFrame: 3 years
measure: Evaluate costs of unnecessary intervention
timeFrame: 3 years
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: McGill University Health Centre, Royal Victoria Hospital
state: Quebec
city: Montréal
country: Canada
facility: Queen Elizabeth Health Complex
state: Quebec
Study officials:
References: