Prospective Sample Collection Study for a Blood-Based cfDNA Methylation Assay for Ovarian Cancer Detection

Official title

Prospective Clinical Validation Study of a Blood-Based cfDNA Methylation Assay for the Detection of Ovarian Cancer

Overview

The goal of this observational study is to learn whether a blood-based cell-free DNA (cfDNA) methylation assay can help detect ovarian cancer, especially early-stage ovarian cancer, in women undergoing clinical evaluation for ovarian tumors or gynecologic diseases. The main questions it aims to answer are: How well can this assay distinguish ovarian cancer from benign gynecologic diseases? How accurately can this assay detect early-stage ovarian cancer and other ovarian tumor subtypes? Researchers will compare the test results from participants with ovarian cancer and participants with benign gynecologic diseases to evaluate the diagnostic performance of the assay. Participants will: Provide blood samples for cfDNA methylation testing Allow researchers to collect clinical and pathological information related to their diagnosis Be grouped according to their final clinical or pathological diagnosis for analysis

Interventions

• Diagnostic test Blood-Based cfDNA Methylation Assay for Ovarian Cancer Detection
  A blood-based diagnostic test performed on plasma samples to analyze a proprietary cfDNA methylation panel for ovarian cancer detection. The assay uses a PCR-based detection method, and test results will be compared with final clinical and/or pathological diagnoses to evaluate diagnostic performance.

Primary outcome measures

• Diagnostic sensitivity [Time frame: From blood sample collection to final clinical and/or pathological diagnosis, up to 6 months]
• Diagnostic specificity [Time frame: From blood sample collection to final clinical and/or pathological diagnosis, up to 6 months]

Secondary outcome measures (5)

• Diagnostic performance of the blood-based cfDNA methylation panel combined with CA125 for early-stage ovarian cancer detection [Time frame: From blood sample collection to final clinical and/or pathological diagnosis, up to 6 months]
• Diagnostic performance of the blood-based cfDNA methylation panel combined with ROMA score for early-stage ovarian cancer detection [Time frame: From blood sample collection to final clinical and/or pathological diagnosis, up to 6 months]
• Detection performance of the blood-based cfDNA methylation panel in borderline ovarian tumors [Time frame: From blood sample collection to final clinical and/or pathological diagnosis, up to 6 months]
• Detection performance of the blood-based cfDNA methylation panel in precursor lesions or high-risk populations [Time frame: From blood sample collection to final clinical and/or pathological diagnosis or clinical classification, up to 6 months]
• Diagnostic performance of the blood-based cfDNA methylation panel across histologic subtypes of ovarian cancer [Time frame: From blood sample collection to final clinical and/or pathological diagnosis, up to 6 months]

Eligibility criteria

Inclusion criteria

• Female participants.
• Participants with an ovarian/adnexal mass who are planned to undergo, for the first time at the current center, surgery or biopsy/pathologic sampling related to the current lesion, with an expected pathologic diagnosis available as the reference standard.
• Imaging evaluation during screening suggests a unilateral or bilateral, unilocular or multilocular cystic-solid or solid ovarian/adnexal mass requiring differential diagnosis.
• An adequate peripheral blood sample can be collected before the first surgery or before initiation of any systemic anti-tumor treatment for the current ovarian/adnexal mass, and the sample can be processed and stored within the required time according to the unified study procedures.
• Clinical data and postoperative pathologic results are expected to be sufficiently complete to provide key information for subsequent analyses.
• The participant or her legally authorized representative voluntarily signs written informed consent after being fully informed.

Exclusion criteria

• The participant has already received systemic anti-tumor treatment for the current ovarian/adnexal lesion under evaluation, such as chemotherapy, targeted therapy, immunotherapy, or radiotherapy, or has already undergone definitive tumor resection or comprehensive staging surgery, and is undergoing surgery only for residual or recurrent lesions.
• No pathologic diagnosis is ultimately obtained for the current ovarian/adnexal mass, or no analyzable pathologic conclusion can be established.
• Imaging findings at screening are highly typical of benign mature cystic teratoma.
• Ovarian cancer combined with another malignant tumor.
• There are obvious noncompliances during sample collection, transport, or processing, resulting in severe hemolysis, contamination, or seriously insufficient sample volume, such that the sample cannot meet quality control requirements for cfDNA methylation testing or subsequent analyses.
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for enrollment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-control

Study locations

China · 1 center

• Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology — Wuhan

Publications

• Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4. PMID 38572751
• Lofton-Day C, Model F, Devos T, Tetzner R, Distler J, Schuster M, Song X, Lesche R, Liebenberg V, Ebert M, Molnar B, Grutzmann R, Pilarsky C, Sledziewski A. DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem. 2008 Feb;54(2):414-23. doi: 10.1373/clinchem.2007.095992. Epub 2007 Dec 18. PMID 18089654
• Nie Y, Gao X, Cai X, Wu Z, Liang Q, Xu G, Liu N, Gao P, Deng J, Xu H, Shen Z, Cao C, Chen F, Zhang N, Song Y, Sun M, Liu C, Zhou G, Han W, Dou J, Xie H, Yao L, Liu Z, Ji G, Wang X, Zhao Q, Shang L, Fan D, Han X, Ren J, Liang H, Wang Z, Wang J, Wu Q, Yu J, Wu K; MAGIS Study Group. Combining methylated SEPTIN9 and RNF180 plasma markers for diagnosis and early detection of gastric cancer. Cancer Comm PMID 37584087
• Liang W, Chen Z, Li C, Liu J, Tao J, Liu X, Zhao D, Yin W, Chen H, Cheng C, Yu F, Zhang C, Liu L, Tian H, Cai K, Liu X, Wang Z, Xu N, Dong Q, Chen L, Yang Y, Zhi X, Li H, Tu X, Cai X, Jiang Z, Ji H, Mo L, Wang J, Fan JB, He J. Accurate diagnosis of pulmonary nodules using a noninvasive DNA methylation test. J Clin Invest. 2021 May 17;131(10):e145973. doi: 10.1172/JCI145973. PMID 33793424
• Xu RH, Wei W, Krawczyk M, Wang W, Luo H, Flagg K, Yi S, Shi W, Quan Q, Li K, Zheng L, Zhang H, Caughey BA, Zhao Q, Hou J, Zhang R, Xu Y, Cai H, Li G, Hou R, Zhong Z, Lin D, Fu X, Zhu J, Duan Y, Yu M, Ying B, Zhang W, Wang J, Zhang E, Zhang C, Li O, Guo R, Carter H, Zhu JK, Hao X, Zhang K. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat Mater. PMID 29035356
• Zhang Q, Hu G, Yang Q, Dong R, Xie X, Ma D, Shen K, Kong B. A multiplex methylation-specific PCR assay for the detection of early-stage ovarian cancer using cell-free serum DNA. Gynecol Oncol. 2013 Jul;130(1):132-9. doi: 10.1016/j.ygyno.2013.04.048. Epub 2013 Apr 25. PMID 23623832

Identifiers

NCT: NCT07593833 · TJ-OVMethy

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗