Developing a Test for the Detection of Ovarian Cancer

Summary

Participation Requirements

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...

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: 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). 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 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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