DOvEEgene: Diagnosing Ovarian and Endometrial Cancer Early Using Genomics (DOvEEgene)

• ClinicalTrials.gov Identifier: NCT02288676
• Recruitment Status: Recruiting
• First Posted: November 11, 2014
• Last Update Posted: May 2, 2024
• Sponsor: McGill University
• Collaborators: McGill University Health Centre/Research Institute of the McGill University Health Centre; Genome Quebec; Jewish General Hospital
• Information provided by (Responsible Party): Dr. Lucy Gilbert, McGill University

Tracking Information

• First Submitted Date: October 28, 2014
• First Posted Date: November 11, 2014
• Last Update Posted Date: May 2, 2024
• Actual Study Start Date: January 2014
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 7, 2018)

Detection of cancer-related mutations [ Time Frame: 3 years ]

Diagnosis ovarian and endometrial cancers by detection of cancer-related mutation taken by brush sample of uterus with high sensitivity and specificity.

Original Primary Outcome Measures (submitted: November 7, 2014)

Detection of cancer-related mutations [ Time Frame: On average, 18 months after clinic visit ]

This outcome will allow us to determine which of the sampling methods most correctly identifies the presence/absence of cancer-related mutations.

Current Secondary Outcome Measures (submitted: September 7, 2018)

• Patient related outcomes including pain and acceptability [ Time Frame: 3 years ]
  Pain scores reported by participants on numeric pain and discomfort scale (NPS). Patients' attitude towards the test including willingness to have it done on an annual basis will be evaluated.
• Risks associated with the DOvEEgene test [ Time Frame: 3 years ]
  Evaluate all risks associated with the DOvEEgene test including complications from the sampling technique as well as unnecessarily interventions resulting from false positive tests.

Original Secondary Outcome Measures (submitted: November 7, 2014)

• Pain scores, reported by participants on Visual Analogue Scale [ Time Frame: During clinic visit, on average 20 minutes ]
  Directly following each collection, participants will be asked to rate their pain on the Visual Analogue Scale.
• Discomfort scores, reported by participants on Visual Analogue Scale [ Time Frame: During clinic visit, on average 20 minutes ]
  Directly following each collection, participants will be asked to rate their discomfort on the Visual Analogue Scale.
• Acceptability of methods, reported by participants [ Time Frame: During clinic visit, on average 20 minutes ]
  Participants will be asked if -hypothetically- they would be willing to undergo such a procedure on an annual basis as a screening test, should it prove to be useful.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: DOvEEgene: Diagnosing Ovarian and Endometrial Cancer Early Using Genomics
• Official Title: DOvEEgene: Diagnosing Ovarian and Endometrial Cancer Early Using Genomics
• Brief Summary: This study aims to develop and validate a test for diagnosing ovarian and endometrial cancers early. It relies on detecting somatic mutations that are associated with these cancers in a biofluids sample taken from the cervix and the uterine cavity.

Detailed Description

For women in high-income countries, ovarian/fallopian tube and endometrial cancers are within the top four cancers in terms of incidence, death and healthcare expenditure. The deaths associated with these cancers are largely caused by stage III/IV disease, for which cure rates have not changed in three decades, despite escalating costs of treatment. Attempts at early diagnosis have been ineffective in reducing mortality, because the high-grade subtypes, which account for the majority of deaths, metastasize while the primary cancer is still small, has not caused symptoms, and is undetectable by imaging or blood tumour markers.

In recent years, the recognition that somatic mutations are early steps in carcinogenesis has led to a shift from tests such as imaging and non-specific blood tumour markers to technology that detects cancer-associated mutations in cervical, uterine, or blood samples. Several DNA-tagging technologies have been shown to be capable of identifying small amount of cancer DNA among thousands of normal cells, the proverbial needle in a haystack.

This investigation aims to develop and validate an in-house developed DNA tagging technology 'DOvEEgene-Haloplex' for the early diagnosis of endometrial and ovarian cancers. The assay pipeline for barcoding and agnostic testing of the biofluids must lend itself to automation and high throughput testing. It must have good sensitivity and more importantly very high specificity, as the only way to corroborate a positive test is to remove the uterus, tubes and ovaries.

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: The participating hospitals run multiple weekly routine gynecology and gynecologic oncology clinics. The cases include women scheduled to undergo surgery for tumor removal, for either proven or suspected upper genital tract cancer. The controls include women scheduled to have a hysterectomy, bilateral salpingectomy (removal of the fallopian tubes) with/without bilateral oophorectomy (removal of the ovaries) to treat benign conditions.

Condition

• Ovarian Neoplasms
• Endometrial Neoplasms
• Endometrial Cancer
• Ovarian Cancer
• Screening
• Safety
• Reduced Mortality
• Reduced Morbidity
• Early Diagnosis

• Intervention: Not Provided

Study Groups/Cohorts

• Case Group
  Participants must have suspected or confirmed upper genital tract cancer (uterine, tubal and ovarian) and must be scheduled to undergo surgery for tumor removal.
• Control Group
  Participants must not be under investigation for any pre-cancerous or cancerous lesions of the genital tract, and must be scheduled for a hysterectomy, bilateral salpingectomy with/without bilateral oopherectomy for presumed benign condition.

Publications *

• Gilbert L, Basso O, Sampalis J, Karp I, Martins C, Feng J, Piedimonte S, Quintal L, Ramanakumar AV, Takefman J, Grigorie MS, Artho G, Krishnamurthy S; DOvE Study Group. Assessment of symptomatic women for early diagnosis of ovarian cancer: results from the prospective DOvE pilot project. Lancet Oncol. 2012 Mar;13(3):285-91. doi: 10.1016/S1470-2045(11)70333-3. Epub 2012 Jan 17.
• Kinde I, Bettegowda C, Wang Y, Wu J, Agrawal N, Shih IeM, Kurman R, Dao F, Levine DA, Giuntoli R, Roden R, Eshleman JR, Carvalho JP, Marie SK, Papadopoulos N, Kinzler KW, Vogelstein B, Diaz LA Jr. Evaluation of DNA from the Papanicolaou test to detect ovarian and endometrial cancers. Sci Transl Med. 2013 Jan 9;5(167):167ra4. doi: 10.1126/scitranslmed.3004952.
• Gilbert L, Revil T, Meunier C, Jardon K, Zeng X, Martins C, Arseneau J, Fu L, North K, Schiavi A, Ehrensperger E, Artho G, Lee T, Morris D, Ragoussis J. The empress of subterfuge: cancer of the fallopian tube presenting with malapropism. Lancet. 2017 Sep 2;390(10098):1003-1004. doi: 10.1016/S0140-6736(17)31586-6. No abstract available.
• Wang Y, Li L, Douville C, Cohen JD, Yen TT, Kinde I, Sundfelt K, Kjaer SK, Hruban RH, Shih IM, Wang TL, Kurman RJ, Springer S, Ptak J, Popoli M, Schaefer J, Silliman N, Dobbyn L, Tanner EJ, Angarita A, Lycke M, Jochumsen K, Afsari B, Danilova L, Levine DA, Jardon K, Zeng X, Arseneau J, Fu L, Diaz LA Jr, Karchin R, Tomasetti C, Kinzler KW, Vogelstein B, Fader AN, Gilbert L, Papadopoulos N. Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers. Sci Transl Med. 2018 Mar 21;10(433):eaap8793. doi: 10.1126/scitranslmed.aap8793.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 18, 2020): 1200
• Original Estimated Enrollment (submitted: November 7, 2014): 280
• Estimated Study Completion Date: October 2026
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Case Inclusion:

• Subjects should have suspected or confirmed cancer of the upper genital tract.
• Participant will undergo surgery for tumour removal.

Control inclusion:

• Subjects should be scheduled to have a hysterectomy, bilateral salpingectomy, with or without bilateral oophorectomy, for presumed benign disease.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Dr. Lucy Gilbert, MD,MSc,FRCOG; (514) 934-1934 ext 34049; lucy.gilbert@mcgill.ca

Contact: Dr. Claudia Martins, PhD; (514) 934-1934 ext 35249; claudia.martins@mcgill.ca

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT02288676
• Other Study ID Numbers: A08-M79-13B
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Dr. Lucy Gilbert, McGill University
• Original Responsible Party: Dr. Lucy Gilbert, McGill University, Professor, Department of Obstetrics and Gynecology
• Current Study Sponsor: McGill University
• Original Study Sponsor: Same as current

Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre
• Genome Quebec
• Jewish General Hospital

Investigators

• Principal Investigator: Dr. Lucy Gilbert, MD,MSc,FRCOG; Professor, McGill University
• Study Director: Dr Ioannis Ragoussis, PhD; Genome Quebec

• PRS Account: McGill University
• Verification Date: May 2024