Screening Test for Detecting Ovarian and Endometrial Cancer

(FemGene Trial)

Recruiting at 1 trial location

Overseen By Lucy Gilbert, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: McGill University

Disqualifiers: Hysterectomy, Pregnant, Nursing, Fertility treatment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

3600 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment DOvEEgene for detecting ovarian and endometrial cancer?

The research highlights the importance of early detection in improving outcomes for ovarian cancer, with strategies like using multiple markers over time showing promise. While CA-125 alone lacks sensitivity, combining it with other markers and advanced analysis could enhance screening effectiveness, which may indirectly support the potential of treatments like DOvEEgene in early cancer detection. ^{1 2 3 4 5}

Is the DOvEEgene test safe for humans?

The research articles provided do not contain specific safety data for the DOvEEgene test or similar tests for detecting ovarian and endometrial cancer. ^{3 6 7 8 9}

How is the DOvEEgene treatment different from other treatments for ovarian and endometrial cancer?

The DOvEEgene treatment is unique because it focuses on early detection of ovarian and endometrial cancers by analyzing DNA for mutations and chromosome changes, which is different from traditional methods like pelvic exams and imaging tests. This approach aims to identify cancers earlier, potentially improving outcomes. ^{10 11 12 13 14}

What is the purpose of this trial?

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.

Eligibility Criteria

The DOvEEgene Phase III Trial is for peri- and postmenopausal women who can understand the study and consent to participate. Women who've had a hysterectomy, are pregnant or nursing, undergoing fertility treatments, or have a recent history of uterine perforation cannot join.

Inclusion Criteria

I understand the study and can give my consent.

I understand the study and can give my consent.

Exclusion Criteria

I have had a hysterectomy.

I have had a recent uterine perforation.

Be undergoing any fertility treatment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic Testing

Participants undergo genomic assay testing using uterine cytological and saliva samples to detect somatic and germline mutations.

3 years

Multiple visits for sample collection and follow-up

Follow-up

Participants are monitored for safety, effectiveness, and quality of life impacts after diagnostic testing.

3 years

Regular follow-up visits and questionnaires

Treatment Details

Interventions

• DOvEEgene

Trial Overview This trial tests the DOvEEgene test, a genomic uterine pap smear designed to detect early-stage ovarian and endometrial cancers in asymptomatic women by identifying specific cancer-related mutations with high accuracy.

Who Is Running the Clinical Trial?

McGill University

Lead Sponsor

Trials

421

Recruited

1,017,000+

McGill University Health Centre/Research Institute of the McGill University Health Centre

Collaborator

Trials

476

Recruited

170,000+

Genome Canada

Collaborator

Trials

17

Recruited

34,400+

Genome Quebec

Collaborator

Trials

8

Recruited

19,800+

Research Institute of the McGill University Health Center

Collaborator

Trials

3

Recruited

5,000+

Molecular diagnostics lab of the MUHC (Optilab)

Collaborator

Trials

1

Recruited

3,600+

Findings from Research

The new ovarian cancer screening strategy using the ROC algorithm demonstrated high specificity (99.8%) and a positive predictive value (PPV) of 19% for detecting primary invasive epithelial ovarian cancer in a study of 13,582 postmenopausal women.

This screening approach is feasible and is currently being implemented in major clinical trials in the UK and the US, indicating its potential for broader application in high-risk populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective study using the risk of ovarian cancer algorithm to screen for ovarian cancer. Menon, U., Skates, SJ., Lewis, S., et al.[2016]

The study analyzed data from 92,843 health plan members and found that using the multivariate assay OVA1 instead of the CA125 test for assessing pelvic masses could lead to modest cost savings of $0.05 per-member per-month for commercially insured patients and $0.01 for Medicare beneficiaries.

Switching to OVA1 not only offers potential economic benefits but also improves diagnostic accuracy for ovarian cancer, allowing for earlier detection and reducing unnecessary referrals to specialists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic Impact of Increased Utilization of Multivariate Assay Testing to Guide the Treatment of Ovarian Cancer: Implications for Payers. Brodsky, BS., Owens, GM., Scotti, DJ., et al.[2022]

Early detection of ovarian cancer is crucial, as over 90% of Stage I cases can be cured, yet currently, less than 25% are diagnosed at this early stage.

While CA-125 is a key serum marker for screening, its isolated values are not sensitive enough; however, monitoring CA-125 levels over time can improve specificity to 99.6%, though sensitivity remains a challenge, indicating the need for more advanced screening strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Status of tumor markers in ovarian cancer screening. Bast, RC.[2016]

Screening for ovarian cancer using CA 125 and transvaginal sonography was found to increase average life expectancy by less than 1 day for a cohort of 40-year-old women in the U.S.

The minimal impact on life expectancy suggests that mass screening for ovarian cancer with these methods may not be an effective health policy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of ovarian cancer screening. A decision analysis model. Schapira, MM., Matchar, DB., Young, MJ.[2022]

Annual screening for ovarian cancer in women with a family history did not significantly reduce overall or disease-specific mortality compared to usual care, based on a study of 78,216 women.

However, women in the screening group were diagnosed at earlier stages of ovarian cancer and had significantly improved survival rates, suggesting that while screening may not lower mortality, it could lead to better outcomes for those diagnosed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovarian cancer screening in menopausal females with a family history of breast or ovarian cancer. Lai, T., Kessel, B., Ahn, HJ., et al.[2018]

In a study of 545 women with a positive family history of ovarian cancer, only two cases of ovarian cancer were detected during 2266 years of follow-up, indicating that annual screening may not be effective in identifying early-stage ovarian cancer in this population.

The study revealed a high recall rate for further testing, particularly in the high-risk group (14%), suggesting that while screening is conducted, it may lead to unnecessary anxiety and additional procedures without significantly improving early detection rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening for ovarian cancer in women with varying levels of risk, using annual tests, results in high recall for repeat screening tests. Nobbenhuis, MA., Bancroft, E., Moskovic, E., et al.[2021]

Screening for ovarian cancer using CA125 and ultrasound in asymptomatic, general-risk postmenopausal women has low positive predictive values, leading to a high rate of false positives and unnecessary surgeries.

The review of 20 studies indicates that there is insufficient evidence to recommend routine ovarian cancer screening in this population, as it does not significantly improve early detection rates and is associated with increased patient anxiety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening postmenopausal women for ovarian cancer: a systematic review. Fung, MF., Bryson, P., Johnston, M., et al.[2022]

A novel screening strategy using CA125 levels every three months, combined with a risk of ovarian cancer algorithm (ROCA), showed improved early-stage detection of ovarian cancer in women at high genetic risk, with 50% of incident cases detected at early stages compared to only 10% in historical controls.

The screening method demonstrated high specificity (92%) for ultrasound referrals, and while the positive predictive value (PPV) was lower (4.6% compared to 10% in general population screening), it still indicated a potentially acceptable level of effectiveness for early detection, suggesting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk - Combined Results from Two Screening Trials. Skates, SJ., Greene, MH., Buys, SS., et al.[2022]

Ovarian cancer has a high mortality rate, with only a 31% five-year survival rate for advanced stages, highlighting the critical need for early diagnosis, which is currently challenging due to the lack of specific symptoms and effective screening methods.

Current screening tests, such as CA-125 and transvaginal ultrasound, do not have the necessary sensitivity and specificity for the general population, and even high-risk women have not shown benefits from screening in prospective studies, indicating a significant public health challenge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovarian cancer screening: a look at the evidence. Fields, MM., Chevlen, E.[2015]

The PapSEEK test can effectively detect endometrial cancers with an 81% success rate and ovarian cancers with a 33% success rate by analyzing DNA for specific mutations and chromosome number changes.

This test has a low false-positive rate, making it a promising tool for early cancer detection in women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening Tool for Gynecologic Cancers Assessed. [2019]

Ovarian cancer is a leading cause of death among gynecological cancers, with 60% to 70% of patients diagnosed at an advanced stage, highlighting the urgent need for early detection methods.

Current screening methods, including pelvic exams, cytology, and imaging, have limitations, but advancements in tumor immunology may offer the best hope for developing effective screening tests for early diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early diagnosis of ovarian cancer. Popkin, DR.[2018]

Ovarian cancer is a significant health concern, being the second most common reproductive system cancer and the leading cause of gynecologic cancer deaths in the U.S., with a low overall 5-year survival rate.

Screening methods such as pelvic examinations, sonography, and serum CA-125 levels are crucial for early diagnosis, with sonography and CA-125 showing the most promise based on extensive studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidemiology and screening of ovarian cancer. Tortolero-Luna, G., Mitchell, MF., Rhodes-Morris, HE.[2005]

The Screenwide study enrolled over 800 women, including those with endometrial and ovarian cancers, BRCA1/2 and MMR pathogenic variant carriers, to evaluate new early detection strategies for gynecological cancers.

Preliminary results indicate that genetic variants in tumors can be effectively detected in minimally invasive samples, with high detection rates of 90% in endometrial aspirates, suggesting a promising approach for early cancer detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Integrated Approach for the Early Detection of Endometrial and Ovarian Cancers (Screenwide Study): Rationale, Study Design and Pilot Study. Peremiquel-Trillas, P., Paytubi, S., Pelegrina, B., et al.[2023]

Ovarian cancer is a leading cause of death among women, with survival rates significantly higher for early-stage diagnosis (95% survival at stage I) compared to advanced stages (15-30% survival).

The OvaCheck test, which utilizes proteomic technology, is expected to provide a highly specific and sensitive method for early detection of ovarian cancer in women at high risk, although it is still awaiting FDA approval for nationwide use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening and detection of ovarian cancer. Breedlove, G., Busenhart, C.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Prospective study using the risk of ovarian cancer algorithm to screen for ovarian cancer. [2016]

2. United States pubmed.ncbi.nlm.nih.gov

Economic Impact of Increased Utilization of Multivariate Assay Testing to Guide the Treatment of Ovarian Cancer: Implications for Payers. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Status of tumor markers in ovarian cancer screening. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

The effectiveness of ovarian cancer screening. A decision analysis model. [2022]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Ovarian cancer screening in menopausal females with a family history of breast or ovarian cancer. [2018]

6. Poland pubmed.ncbi.nlm.nih.gov

Screening for ovarian cancer in women with varying levels of risk, using annual tests, results in high recall for repeat screening tests. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Screening postmenopausal women for ovarian cancer: a systematic review. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk - Combined Results from Two Screening Trials. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Ovarian cancer screening: a look at the evidence. [2015]

10. United States pubmed.ncbi.nlm.nih.gov

Screening Tool for Gynecologic Cancers Assessed. [2019]

11. Canada pubmed.ncbi.nlm.nih.gov

Early diagnosis of ovarian cancer. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Epidemiology and screening of ovarian cancer. [2005]

13. Switzerland pubmed.ncbi.nlm.nih.gov

An Integrated Approach for the Early Detection of Endometrial and Ovarian Cancers (Screenwide Study): Rationale, Study Design and Pilot Study. [2023]

14. United States pubmed.ncbi.nlm.nih.gov

Screening and detection of ovarian cancer. [2015]