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Developing a Test for the Detection of Ovarian Cancer

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ClinicalTrials.gov Identifier: NCT04794322
Recruitment Status : Recruiting
First Posted : March 12, 2021
Last Update Posted : May 3, 2022
Sponsor:
Collaborators:
Johns Hopkins University
Fred Hutchinson Cancer Center
Anne Arundel Health System Research Institute
University of Arkansas
National Cancer Institute (NCI)
Kaiser Permanente
McGill University
M.D. Anderson Cancer Center
Swedish Medical Center
TwinStrand Biosciences
Information provided by (Responsible Party):
Steven Skates, Massachusetts General Hospital

Brief Summary:

The study aims to develop a test for early detection of ovarian cancer using DNA from a growth involving the ovary found in a washing of the uterus (womb), and proteins found in the blood. The samples of the wash and the blood will be taken before surgery. After surgery, doctors will determine whether the participant had ovarian cancer or a benign disease of the ovaries. The tests of the washings and the blood will be examined to see how much the participants with ovarian cancer can be separated from the participants with a benign ovarian disease by the tests. Small amounts from the washing and the blood samples will be sent to four sites for analysis.

Statistical analyses of these data will compare tumor DNA found in the washing of the uterus with proteins in the blood to detect cases of ovarian cancer. The primary goal is to find tests that are mostly positive for cases of ovarian cancer and mostly negative for patients with benign disease. It is hoped that if the tests work for participants with symptoms of the disease that these tests will also work when testing women who have no symptoms. A new study would be needed to see if the tests worked in this situation. If the tests work, this could lead to increasing the number of cases detected in early stage disease and decreasing the number of cases detected in late stage disease. If this change in late stage is large, it will likely reduce deaths due to ovarian cancer.


Condition or disease Intervention/treatment
Ovarian Neoplasms Ovarian Epithelial Carcinoma Fallopian Tube Neoplasms High Grade Ovarian Serous Adenocarcinoma Stage I Ovarian Cancer Stage II Ovarian Cancer Stage III Ovarian Cancer AJCC v8 Stage IIIA Ovarian Cancer AJCC v8 Stage IIIA1 Ovarian Cancer AJCC v8 Stage IIIA2 Ovarian Cancer AJCC v8 Stage IIIB Ovarian Cancer AJCC v8 Stage IIIC Ovarian Cancer AJCC v8 Stage IV Ovarian Cancer AJCC v8 Stage IVA Ovarian Cancer AJCC v8 Stage IVB Ovarian Cancer AJCC v8 Diagnostic Test: Uterine lavage, or a wash of the womb Diagnostic Test: Blood sample Diagnostic Test: Pap smear

Detailed Description:

The study aims to elucidate the relative contributions to detection of ovarian cancer from tumor DNA in uterine lavage (UL) and protein biomarkers from blood using newly available detection and sample collection technologies. In this document, the term "ovarian cancer" includes fallopian tube cancer. In the first cohort, the study will enroll 200 participants. Enrolling participants prior to surgical diagnosis (e.g. laparoscopy or paracentesis) ensures the study will be "Prospective Collection of Samples, Blinded Evaluation" (PRoBE) compliant. The expectation is that ~50 of these participants will have pathologically confirmed ovarian cancer. In a second cohort, 50 participants will be enrolled. Based on published reports, it is expected that ~5 participants will have microscopic or low volume ovarian cancer. In each cohort, the participants with a pathologic invasive epithelial ovarian cancer diagnosis will be defined as Cases and participants without any ovarian cancer, primary peritoneal cancer (PPC), or other cancer identified due to the surgery, will be defined as Controls. Other cancer groups are: (i) PPC, (ii) non-invasive serous tubal intraepithelial carcinoma (STIC) lesions, (iii) non-epithelial ovarian cancers, and (iv) non-ovarian cancers.

Two sites will sequence DNA obtained from uterine lavages to detect tumor-derived DNA (tDNA): one will carry out Duplex Sequencing of TP53 and the second site will carry out Haloplex sequencing of an 18-gene panel. Two other sites will assay serum proteins: the first will use clinical grade assays for CA125 and HE4, and the second will use research grade assays for these two proteins plus four additional protein biomarker candidates. Statistical analyses of these data will evaluate the relative utility of tDNA and plasma proteins to detect Cases (sensitivity) while limiting detection of Controls (specificity) in these two cohorts. Remaining DNA from UL and blood based biospecimens in form of plasma, serum, and buffy coat will be stored at a biorepository at NCI Frederick for future biomarker investigations which include (but are not limited to) other methods of detecting tDNA from UL, tDNA from plasma, exosomal markers, and additional blood-based and UL biomarker candidates.

Primary objectives:

  1. To collect samples from 200 participants with suspected ovarian cancer (of which ~50 or more are expected to have pathologically confirmed ovarian cancer) and 50 participants undergoing a risk-reducing salpingo-oophorectomy (of which ~5 are expected to have microscopic or low volume ovarian cancer).
  2. To test the tDNA from uterine lavage samples for tumor-derived TP53 mutations, using Duplex sequencing, and for potential abnormalities in an 18-gene panel, using Haloplex sequencing
  3. To test the serum proteins with two assays: the first will use clinical grade assays for CA125 and HE4, and the second will use research grade assays for these two proteins plus four additional protein biomarker candidates.

Outline: Participants undergo two blood draws (one required, one optional) up to 31 days before surgery and a uterine lavage at the time of planned surgery. The tDNA and serum proteins are then extracted from the samples and sent for analysis.

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Study Type : Observational
Estimated Enrollment : 250 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Ovarian Cancer Detection by Uterine Lavage DNA and Serum Proteins: a Phase 2 Biomarker Study
Actual Study Start Date : April 13, 2020
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2025


Group/Cohort Intervention/treatment
Pelvic Mass Cohort (cohort #1)
200 participants scheduled for surgery for suspected ovarian cancer due to a pelvic mass but without a confirmed tissue or cytology diagnosis.
Diagnostic Test: Uterine lavage, or a wash of the womb
Uterine lavage is performed during surgery using a flexible, 3-way balloon tipped catheter. The catheter is inserted through the cervix, the balloon expanded and the uterine cavity lavaged using 10 cc of sterile saline which is collected, processed and stored for later analysis.

Diagnostic Test: Blood sample
Participants undergo two blood draws (one required, one optional) up to 31 days before surgery

Diagnostic Test: Pap smear
Participants undergo a standard Papanicolaou smear to collect cells and fluid from the cervix.

BRCA1/2 Carriers Cohort (cohort #2)
50 participants with an inherited BRCA1 or BRCA2 deleterious mutation without suspected ovarian cancers who are scheduled for risk-reducing salpingo-oophorectomy (RRSO) to remove ovaries and fallopian tubes.
Diagnostic Test: Uterine lavage, or a wash of the womb
Uterine lavage is performed during surgery using a flexible, 3-way balloon tipped catheter. The catheter is inserted through the cervix, the balloon expanded and the uterine cavity lavaged using 10 cc of sterile saline which is collected, processed and stored for later analysis.

Diagnostic Test: Blood sample
Participants undergo two blood draws (one required, one optional) up to 31 days before surgery

Diagnostic Test: Pap smear
Participants undergo a standard Papanicolaou smear to collect cells and fluid from the cervix.




Primary Outcome Measures :
  1. Genomic biomarkers assessing mutations and methylation of tumor DNA, and protein biomarkers measured as the concentration of a protein in pg/mL, both types of biomarkers measured in the collected biospecimens. [ Time Frame: Through study completion, an average of three years ]
    Biomarkers that distinguish between ovarian cancer and benign ovarian disease


Biospecimen Retention:   Samples With DNA
  • Serum (red-top tubes)
  • EDTA plasma (purple-top tubes)
  • Uterine Lavage supernatant (conical tube)
  • Uterine Lavage filter (conical tube)
  • Uterine Lavage cell pellet (conical tube)
  • Buffy coat (purple-top tubes)
  • Tissue sections


Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Cohorts will be selected from patients scheduled for ovarian disorder-related surgeries across six sites: Massachusetts General Hospital in Boston, Massachusetts; Anne Arundel Health System in Annapolis, Maryland; Johns Hopkins University School of Medicine in Baltimore, Maryland; Kaiser Permanente - San Francisco in San Francisco, California; the Swedish Medical Center in Seattle, Washington; and the University of Arkansas for Medical Sciences in Little Rock, Arkansas.
Criteria

Inclusion Criteria:

  • Has intact uterus (no history of uterine ablation, tubal ligation or bilateral salpingectomy)
  • Cohort 1 (n=200 participants): Women scheduled for surgery or diagnostic laparoscopy for suspected but undiagnosed ovarian/fallopian tube cancer
  • Cohort 2 (n=50 participants): Known BRCA1 or BRCA2 mutation carrier scheduled for risk-reducing salpingo-oophorectomy

Exclusion Criteria:

  • Current tissue or cytology diagnostic procedure positive for ovary cancer or any cancer
  • Inability to provide informed consent
  • Age less than 30 years
  • Inability to obtain the minimum amount of blood
  • Inability to obtain the minimum amount of uterine lavage sample
  • At risk if blood were drawn (e.g. hemophilia, serious anemia- Hb less than 8.0 gm/dL)
  • Prior history of known ovarian or endometrial cancer
  • Treatment less than 1 year (excluding hormonal therapy) for cancer that spread beyond its origin
  • History of untreated high-grade cervical dysplasia (CIN3)
  • History of treated high grade cervical dysplasia (CIN3) with a cytologically abnormal pap smear within the past year. If there is no post treatment Pap smear in the medical record, perform a Pap smear prior to the day of surgery. If this Pap smear is abnormal, the participant is ineligible.
  • Currently pregnant
  • Known Lynch syndrome

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04794322


Contacts
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Contact: Jackie Dahlgren 206 667 3438 jdahlgre@fredhutch.org

Locations
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United States, Arkansas
University of Arkansas for Medical Sciences Recruiting
Little Rock, Arkansas, United States, 72205
Contact: Beth Scanlan    501-686-8274    BScanlan@uams.edu   
Principal Investigator: Kristin Zorn, MD         
United States, California
Kaiser Permanente - San Francisco Not yet recruiting
San Francisco, California, United States, 94115
Contact: Isabel Perez    415-833-3480    isabel.p.perez@kp.org   
Principal Investigator: Christine Garcia, MD         
United States, Maryland
Anne Arundel Health System Recruiting
Annapolis, Maryland, United States, 21401
Contact: Jaci Miller    443-481-5738    jmiller9@aahs.org   
Principal Investigator: Monica Jones, MD         
Johns Hopkins University School of Medicine Recruiting
Baltimore, Maryland, United States, 21218
Contact: Rebecca Stone, MD       rstone15@jhmi.edu   
Principal Investigator: Rebecca Stone, MD         
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Tina Colella    617-643-5150    tcolella@partners.org   
Principal Investigator: Amy Bregar, MD         
United States, Washington
The Swedish Hospital Recruiting
Seattle, Washington, United States, 98122
Contact: Robert Pearhill    206-667-3278    rpearhil@fredhutch.org   
Principal Investigator: Charles Drescher, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Johns Hopkins University
Fred Hutchinson Cancer Center
Anne Arundel Health System Research Institute
University of Arkansas
National Cancer Institute (NCI)
Kaiser Permanente
McGill University
M.D. Anderson Cancer Center
Swedish Medical Center
TwinStrand Biosciences
Investigators
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Study Director: Christos Patriotis, PhD National Cancer Institute (NCI)
Publications:
Jacobs IJ, Menon U, Ryan A, Gentry-Maharaj A, Burnell M, Kalsi JK, Amso NN, Apostolidou S, Benjamin E, Cruickshank D, Crump DN, Davies SK, Dawnay A, Dobbs S, Fletcher G, Ford J, Godfrey K, Gunu R, Habib M, Hallett R, Herod J, Jenkins H, Karpinskyj C, Leeson S, Lewis SJ, Liston WR, Lopes A, Mould T, Murdoch J, Oram D, Rabideau DJ, Reynolds K, Scott I, Seif MW, Sharma A, Singh N, Taylor J, Warburton F, Widschwendter M, Williamson K, Woolas R, Fallowfield L, McGuire AJ, Campbell S, Parmar M, Skates SJ. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2016 Mar 5;387(10022):945-956. doi: 10.1016/S0140-6736(15)01224-6. Epub 2015 Dec 17. Erratum in: Lancet. 2016 Mar 5;387(10022):944. Erratum in: Lancet. 2016 Mar 5;387(10022):944.
Pepe MS "The Statistical Evaluation of Medical Tests for Classification and Prediction". Oxford University Press (2003)

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Responsible Party: Steven Skates, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT04794322    
Other Study ID Numbers: 20-450
5U01CA152990 ( U.S. NIH Grant/Contract )
First Posted: March 12, 2021    Key Record Dates
Last Update Posted: May 3, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual participant data is not anticipated to be shared.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Steven Skates, Massachusetts General Hospital:
Uterine Lavage
Tumor DNA
Serum proteins
Ovarian neoplasms
Ovarian epithelial carcinoma
Ovarian cancer
Ovarian epithelial cancer
Neoplasms
Ovarian diseases
Early detection
Additional relevant MeSH terms:
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Carcinoma
Neoplasms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Cystadenocarcinoma, Serous
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Fallopian Tube Diseases