Screening Test for Detecting Ovarian and Endometrial Cancer
(FemGene Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: McGill University
Disqualifiers: Hysterectomy, Pregnant, Nursing, Fertility treatment, others
No Placebo Group
Trial Summary
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.
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.
12345Is 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.
36789How 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.
1011121314Eligibility 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
+2 more
Trial 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
Participant Groups
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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
McGill University Health Centre, Royal Victoria HospitalMontreal, Canada
Queen Elizabeth Health ComplexMontréal, Canada
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Who Is Running the Clinical Trial?
McGill UniversityLead Sponsor
McGill University Health Centre/Research Institute of the McGill University Health CentreCollaborator
Genome CanadaCollaborator
Genome QuebecCollaborator
Research Institute of the McGill University Health CenterCollaborator
Molecular diagnostics lab of the MUHC (Optilab)Collaborator
References
Prospective study using the risk of ovarian cancer algorithm to screen for ovarian cancer. [2016]To evaluate prevalence screening in the first prospective trial of a new ovarian cancer screening (OCS) strategy (risk of ovarian cancer or ROC algorithm) on the basis of age and CA125 profile.
Economic Impact of Increased Utilization of Multivariate Assay Testing to Guide the Treatment of Ovarian Cancer: Implications for Payers. [2022]Ovarian cancer is the eighth most common cancer among women, but ranks fifth in cancer-related causes of death, the majority of which are detected in late stages, after the cancer has metastasized. The CA125 test is the standard of care for assessing suspicious pelvic masses. However, the primary use of CA125 is to monitor treatment progress rather than to screen for disease, and its sensitivity is exceedingly low, unlike the multivariate assay OVA1. A cost-effective treatment of ovarian cancer requires early and accurate diagnosis of pelvic masses and reduced referrals of patients with benign tumors to a gynecologic oncologist.
Status of tumor markers in ovarian cancer screening. [2016]One of the most promising approaches to management of ovarian cancer is early detection. Stage I ovarian cancer can be cured with currently available therapy in more than 90% of patients. However, fewer than 25% of ovarian cancers are currently detected in stage I. Detection of a greater fraction of cancers at an early stage might improve clinical outcome. Given a prevalence of one patient with ovarian cancer among 2,500 asymptomatic postmenopausal women in the general population, a successful screening strategy must have a sensitivity of more than 75% and a specificity of more than 99.6% to achieve a positive predictive value of 10%. Approaches to screening include transvaginal sonography, serum markers, and two-stage strategies that use alterations in serum markers to prompt sonographic examination. Among the serum markers, CA-125 has been studied most extensively. Isolated values of CA-125 lack adequate sensitivity or specificity, but when monitored over time, serial CA-125 values can achieve a specificity of 99.6%. However, sensitivity is limited and CA-125 may only be expressed by 80% of early-stage cancers. Multiple markers may exhibit greater specificity when studied over time. To combine multiple markers, more sophisticated mathematical analysis will be required. At present, screening women at conventional risk should be restricted to clinical trials. In the future, however, screening for ovarian cancer may reduce the morbidity and mortality of this disease.
The effectiveness of ovarian cancer screening. A decision analysis model. [2022]To estimate the effectiveness of ovarian cancer screening with CA 125 and transvaginal sonography.
Ovarian cancer screening in menopausal females with a family history of breast or ovarian cancer. [2018]To determine whether annual screening reduces ovarian cancer mortality in women with a family history of breast or ovarian cancer.
Screening for ovarian cancer in women with varying levels of risk, using annual tests, results in high recall for repeat screening tests. [2021]We assessed ovarian cancer screening outcomes in women with a positive family history of ovarian cancer divided into a low-, moderate- or high-risk group for development of ovarian cancer.
Screening postmenopausal women for ovarian cancer: a systematic review. [2022]To assess ovarian cancer screening in asymptomatic, general-risk postmenopausal women. Outcomes of interest were the screening tests assessed (predictive values, sensitivity, and specificity), the stage of screen-detected disease at diagnosis, psychological effects of screening, and survival.
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]Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL.Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls.Results: Specificity for ultrasound referral was 92% versus 90% (P = 0.0001), and PPV was 4.6% versus 10% (P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent = 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years).Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation. Clin Cancer Res; 23(14); 3628-37. ©2017 AACR.
Ovarian cancer screening: a look at the evidence. [2015]In 2005, more than 22,000 American women were diagnosed with ovarian cancer and 16,000 women died from the disease. The five-year relative survival rate for stage III and IV disease is 31%, and the five-year relative survival rate for stage I is 95%. Early diagnosis should lower the fatality rate. Unfortunately, early diagnosis is difficult because of the physically inaccessible location of the ovaries, the lack of specific symptoms in early disease, and the limited understanding of ovarian oncogenesis. Screening tests for ovarian cancer need high sensitivity and specificity to be useful because of the low prevalence of undiagnosed ovarian cancer. Because currently available screening tests do not achieve high levels of sensitivity and specificity, screening is not recommended for the general population. The theoretical advantage of screening is much higher for women at high risk (such as those with a strong family history of ovarian cancer and those with BRCA 1 or BRCA 2 mutations). However, even for women at high risk, no prospective studies have shown benefits of screening. The public health challenge is that 90% of ovarian cancer occurs in women who are not in an identifiable high-risk group, and most women are diagnosed with advanced-stage disease. Currently available tests (CA-125, transvaginal ultrasound, or a combination of both) lack the sensitivity and specificity to be useful in screening the general population. Ongoing clinical trials are assessing whether new tumor markers, including those generated by proteomic and genomic studies, will prove useful.
Screening Tool for Gynecologic Cancers Assessed. [2019]Researchers have developed a test called PapSEEK that detects endometrial and ovarian cancers by analyzing DNA samples for mutations and aberrations in chromosome number. In a large, retrospective study, the test detected 81% of endometrial cancers and 33% of ovarian cancers with a low false-positive rate.
Early diagnosis of ovarian cancer. [2018]Ovarian cancer is the most common fatal gynecologic malignant disease. Unfortunately 60% to 70% of patients present initially with advanced disease. Progress in the treatment of this condition will be made only if it can be diagnosed early. Pelvic examination is still the best screening test despite attempts to make an early diagnosis with the use of cytology, ultrasonography, and serum determinations for fibrin degradation product; haptoglobin, protein-bound fucose and tumour-associated antigens. The best prospect for a screening test for ovarian cancer probably lies in the field of tumour immunology.
Epidemiology and screening of ovarian cancer. [2005]Ovarian cancer is the second most common neoplasm of the female reproductive system and the leading cause of death from gynecologic cancer in the United States. The overall 5-year survival rate continues to be low. Risk factors associated with ovarian cancer are age, race, nulliparity, infertility, history of endometrial or breast cancer, and family history of ovarian cancer. The diagnosis of ovarian cancer could benefit from screening. Screening methods for ovarian cancer include pelvic examination, abdominal and transvaginal sonography, color flow Doppler, and serum CA-125 levels. Sonography and CA-125 are the most promising and most extensively studied.
An Integrated Approach for the Early Detection of Endometrial and Ovarian Cancers (Screenwide Study): Rationale, Study Design and Pilot Study. [2023]Screenwide is a case-control study (2017−2021) including women with incident endometrial and ovarian cancers (EC and OC), BRCA1/2 and MMR pathogenic variant carriers, and age-matched controls from three centers in Spain. Participants completed a personal interview on their sociodemographic factors, occupational exposure, medication, lifestyle, and medical history. We collected biological specimens, including blood samples, self-collected vaginal specimens, cervical pap-brush samples, uterine specimens, and, when available, tumor samples. The planned analyses included evaluation of the potential risk factors for EC/OC; evaluation of molecular biomarkers in minimally invasive samples; evaluation of the cost-effectiveness of molecular tests; and the generation of predictive scores to integrate different epidemiologic, clinical, and molecular factors. Overall, 182 EC, 69 OC, 98 BRCA pathogenic variant carriers, 104 MMR pathogenic variant carriers, and 385 controls were enrolled. The overall participation rate was 85.7%. The pilot study using 61 samples from nine EC cases and four controls showed that genetic variants at the variant allele fraction > 5% found in tumors (n = 61 variants across the nine tumors) were detected in paired endometrial aspirates, clinician-collected cervical samples, and vaginal self-samples with detection rates of 90% (55/61), 79% (48/61), and 72% (44/61) by duplex sequencing, respectively. Among the controls, only one somatic mutation was detected in a cervical sample. We enrolled more than 800 women to evaluate new early detection strategies. The preliminary data suggest that our methodological approach could be useful for the early detection of gynecological cancers.
Screening and detection of ovarian cancer. [2015]According to the National Cancer Institute, ovarian cancer is the sixth most common cancer in women and the leading cause of death from gynecologic malignancies. Most often the disease is advanced before symptoms are evident. It is estimated that only 15% to 30% of women in advanced stages will survive 5 years, whereas, of women in stage I at the time of diagnosis, 95% are likely to be alive in 5 years, and most are cured following surgery. Current screening techniques recommended for women with known strong risk factors include combination transvaginal sonography with cancer antigen (CA-125). Transvaginal sonography and serum CA-125 have limited diagnostic predictability. A new early detection method that uses proteomic technology will soon be available. The OvaCheck test, as researchers purport, is a highly specific and sensitive early detection method for ovarian cancer in women with strong risk factors. The Food and Drug Administration has yet to approve nationwide marketing of OvaCheck for early detection, because trials are not yet complete. Anticipated commercial availability is scheduled for early 2005.