CA 125 Blood Test for Early Detection of Ovarian Cancer

Recruiting at 10 trial locations

Overseen By Gwen H. Corrigan

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: High cancer risk, Psychiatric conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

8000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if specific blood tests can help detect ovarian cancer early in women at low risk. Participants will have blood drawn to check for markers that might indicate early signs of ovarian cancer. If certain levels are detected, additional tests, such as another blood draw or an ultrasound, might be needed later. Women who are postmenopausal, have at least one ovary, are cancer-free, and have not had recent cancer treatment might be suitable for this study. Participants will also complete a questionnaire, which may include a Pictorial Educational Tool or a Verbal Counseling Tool, to gather additional information.

As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research in early cancer detection.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking SERMS (like tamoxifen or aromatase inhibitors), you are not excluded from participating.

What prior data suggests that this method is safe for early detection of ovarian cancer?

Research has shown that the CA 125 blood test is a reliable method for diagnosing and managing ovarian cancer. Many studies have identified this test as often being the first step in checking for symptoms of ovarian cancer. It is generally safe, requiring only a small blood sample, about 3-4 tablespoons, which is a common medical procedure.

The test measures the level of CA 125, a protein that can be elevated in some women with ovarian cancer. While the test itself is safe, high CA 125 levels do not always indicate cancer, and not all ovarian cancers will cause elevated CA 125 levels. Thus, while helpful, the test is not perfect on its own.

Overall, the CA 125 test poses no major safety concerns for participants. It involves a simple blood draw, a standard procedure in many medical tests. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new method for early detection of ovarian cancer using the CA 125 blood test and additional tumor markers like HE4 and Osteopontin. Unlike traditional methods that primarily rely on imaging and later-stage symptom detection, this approach aims to catch the disease in its earliest stages through blood analysis. By potentially identifying ovarian cancer sooner, this method could lead to earlier interventions and improved outcomes for patients.

What evidence suggests that this method is effective for early detection of ovarian cancer?

Research has shown that the CA 125 blood test can help detect ovarian cancer. Approximately 80% of individuals with ovarian cancer exhibit higher than normal CA 125 levels, making it a useful indicator for identifying potential cancer. In this trial, participants will undergo CA 125 analysis alongside other tumor markers to enhance early detection efforts. It is important to note that CA 125 is the only tumor marker officially recommended for diagnosing and managing ovarian cancer. However, it can sometimes produce false positives, as not every high reading indicates cancer. This test is part of a broader strategy to detect ovarian cancer early and improve treatment outcomes. ^{1 3 6 7 8}

Who Is on the Research Team?

Denise Nebgen, MD, PHD

Principal Investigator

The University of Texas MD Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for women aged 50-75 who are postmenopausal, have at least one ovary, and haven't had cancer or cancer treatments in the last year. Participants must be willing to take annual blood tests and possibly a transvaginal ultrasound if needed. They should not have conditions preventing informed consent, both ovaries removed, high genetic risk for ovarian cancer, or active non-ovarian malignancies.

Inclusion Criteria

Willingness to return for CA 125 blood tests annually or earlier if indicated

Willingness to return to undergo transvaginal ultrasound if indicated

I have not had a menstrual period for at least 12 months.

Exclusion Criteria

I have had both of my ovaries removed.

I am at high risk for ovarian cancer due to my family history.

I have an active cancer that is not ovarian cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Initial Assessment

Participants have blood drawn for CA-125 and other tumor markers, and complete medical and symptom questionnaires

1 day

1 visit (in-person)

Monitoring

Participants return for blood tests and possibly a transvaginal ultrasound based on CA-125 levels

Varies (3 months, 6 weeks, or 1 year)

1 visit every 3 months, 6 weeks, or 1 year (in-person)

Follow-up

Participants are monitored for safety and effectiveness after initial assessments and interventions

3 years

Annual visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Questionnaire

Trial Overview The study is testing whether a blood test called CA-125 can help detect ovarian cancer early in low-risk women. Participants will complete questionnaires and undergo regular CA-125 blood tests with follow-up procedures like ultrasounds if results suggest further examination is necessary.

How Is the Trial Designed?

Group I: CA 125 Analysis Experimental Treatment 1 Intervention

Experimental: CA 125, HE4, HE4 antigen autoantibody complexes, and Osteopontin Analysis Participants will have blood (3-4 tablespoons) drawn for CA125 and other tumor markers. Depending on CA-125 level and other tumor markers: Blood (3-4 tablespoons) drawn for CA-125 testing and other tumor markers in 1 year. Blood (3-4 tablespoons) drawn for CA-125 testing and other tumor markers in 3 months, OR Blood (3-4 tablespoons) drawn for CA-125 testing and other tumor markers, and a transvaginal ultrasound in 6 weeks +/- 2 weeks.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Golfers Against Cancer

Collaborator

Trials

2

Recruited

8,000+

Published Research Related to This Trial

In a study of 50,780 women, CA125 levels were found to be a useful biomarker for detecting ovarian cancer, especially in women aged 50 and older, where 15.2% of those with elevated levels had ovarian cancer.

The study also highlighted that high CA125 levels could indicate non-ovarian cancers, with 20.4% of women aged 50 and older diagnosed with non-ovarian cancer despite having elevated CA125 levels, emphasizing the need for careful evaluation in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The diagnostic performance of CA125 for the detection of ovarian and non-ovarian cancer in primary care: A population-based cohort study. Funston, G., Hamilton, W., Abel, G., et al.[2021]

Screening for ovarian cancer using CA 125 and transvaginal sonography was found to increase average life expectancy by less than 1 day for a cohort of 40-year-old women in the U.S.

The minimal impact on life expectancy suggests that mass screening for ovarian cancer with these methods may not be an effective health policy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of ovarian cancer screening. A decision analysis model. Schapira, MM., Matchar, DB., Young, MJ.[2022]

In a study of 456 women diagnosed with ovarian cancer, those with normal CA125 levels (<35 U/ml) had a longer median time to diagnosis (64 days) compared to those with abnormal levels (35 days), indicating that abnormal levels may prompt quicker medical responses.

Women with normal CA125 levels were more likely to be diagnosed at an early stage (86%) compared to those with abnormal levels (35%), suggesting that normal CA125 results are associated with less aggressive tumor types and better prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CA125 test result, test-to-diagnosis interval, and stage in ovarian cancer at diagnosis: a retrospective cohort study using electronic health records. Funston, G., Mounce, LT., Price, S., et al.[2021]

Current screening methods for ovarian cancer, such as CA 125 and transvaginal ultrasonography, have not been proven effective for widespread use to reduce mortality, and may even increase morbidity and mortality, highlighting the need for further research.

For early-stage ovarian cancer, women with stage IA grade 1 and most IB grade 1 do not need postoperative adjuvant therapy, while those with higher stages (II, III, and IV) should receive postoperative chemotherapy, emphasizing the importance of tailored treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

National Institutes of Health Consensus Development Conference Statement. Ovarian cancer: screening, treatment, and follow-up. [2022]

Ovarian cancer is a leading cause of cancer death among women, with over 20,000 diagnoses and approximately 15,000 deaths annually in the USA, primarily due to late-stage diagnosis and lack of effective screening methods.

Current research suggests that using a multimarker approach, rather than relying solely on the CA-125 protein, could significantly improve the early detection of ovarian cancer, potentially leading to the development of a reliable screening test.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple biomarker panels for early detection of ovarian cancer. Yurkovetsky, ZR., Linkov, FY., E Malehorn, D., et al.[2015]

CA 125 levels are often elevated in women with ovarian cancer before symptoms appear, making it a useful marker for early detection, although using a cutoff of 30 U/mL has good sensitivity but poor specificity.

Combining CA 125 testing with transvaginal ultrasonography or a mathematical algorithm to analyze changes in CA 125 levels can improve the accuracy of ovarian cancer screening, and two major trials are currently assessing the impact of these strategies on mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of CA 125 in screening for ovarian cancer. Rosenthal, AN., Jacobs, IJ.[2022]

OVA1, a multivariate index assay, significantly improves the detection of ovarian malignancies in patients with low-risk CA125 levels, identifying over 50% of cancers in premenopausal women and 63% of early-stage cancers that CA125 misses.

In this study of 2305 patients, OVA1 demonstrated a sensitivity of 59% and successfully detected various ovarian cancer subtypes, suggesting it could enhance early detection and referral to specialists, potentially improving survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvaging Detection of Early-Stage Ovarian Malignancies When CA125 Is Not Informative. Dunton, CJ., Hutchcraft, ML., Bullock, RG., et al.[2021]

In a study of 100 ovarian cancer patients, a low pre-operative CA-125 level did not correlate with better survival outcomes, indicating it may not be a reliable prognostic marker.

Monitoring CA-125 levels during treatment was effective in assessing patient response, with significant decreases in CA-125 associated with better survival, and increases often indicating disease progression up to 9 months before clinical symptoms appeared.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CA-125 monitoring in the management of ovarian cancer. Bruzzone, M., Onetto, M., Campora, E., et al.[2004]

In a study of 142 patients with epithelial ovarian cancer, higher preoperative CA 125 levels were significantly associated with worse outcomes, including higher tumor stage, grade, and the presence of ascites, indicating that CA 125 can be a useful biomarker for assessing disease severity.

While preoperative CA 125 levels can predict disease-specific survival, they are not reliable for predicting optimal cytoreduction, as levels below 500 U/mL only had a positive predictive value of 82% for successful surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative CA 125 levels: an independent prognostic factor for epithelial ovarian cancer. Cooper, BC., Sood, AK., Davis, CS., et al.[2019]

A new dichotomous prediction model for CA125 levels, which includes factors like age, race, and body mass index, showed moderate effectiveness in distinguishing between normal and elevated CA125 levels in postmenopausal women, with an area under the curve (AUC) of 0.80 in validation datasets.

The linear prediction model explained only 5% of the variability in CA125 levels, indicating that while personal characteristics can help improve CA125's predictive power, further research is needed to identify additional factors that could enhance its accuracy as a screening biomarker for ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and validation of circulating CA125 prediction models in postmenopausal women. Sasamoto, N., Babic, A., Rosner, BA., et al.[2022]

Despite the 2009 trial showing that CA-125 tests do not improve survival and can decrease quality of life, their use in ovarian cancer surveillance remains high, with 91% of patients undergoing multiple tests from 2010-2012.

The study found no significant change in the time to retreatment after CA-125 levels doubled before and after the 2009 trial, indicating that the routine use of these tests may not provide clinical benefits, while incurring substantial costs estimated at nearly $17 million annually when including CT scans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of CA-125 Tests and Computed Tomographic Scans for Surveillance in Ovarian Cancer. Esselen, KM., Cronin, AM., Bixel, K., et al.[2022]

Early detection of ovarian cancer is crucial, as over 90% of Stage I cases can be cured, yet currently, less than 25% are diagnosed at this early stage.

While CA-125 is a key serum marker for screening, its isolated values are not sensitive enough; however, monitoring CA-125 levels over time can improve specificity to 99.6%, though sensitivity remains a challenge, indicating the need for more advanced screening strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Status of tumor markers in ovarian cancer screening. Bast, RC.[2016]

A significant portion of physicians (40.4%) mistakenly believe that CA-125 and transvaginal ultrasonography (TVS) are effective for screening ovarian cancer in asymptomatic, average-risk women, highlighting a gap in knowledge among healthcare providers.

Only about one third of women are aware of the CA-125 test, and educational efforts are needed to inform both providers and the public about the lack of evidence supporting its use and the potential harms of unnecessary screening for ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physician knowledge and awareness of CA-125 as a screen for ovarian cancer in the asymptomatic, average-risk population. Stewart, SL., Rim, SH., Gelb, CA.[2016]

The study analyzed 15,093 serum samples and found that the CA 125 test had a detection rate of only 21-33% for ovarian cancer, indicating it is not effective as a standalone screening test.

Although there were some case-control differences in CA 125 levels before diagnosis, they were not significant enough to warrant its use as a reliable screening method for ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CA 125 as a screening test for ovarian cancer. Hakama, M., Stenman, UH., Knekt, P., et al.[2017]

Current screening methods for ovarian cancer, such as transvaginal ultrasound and the CA125 biomarker, lack proven efficacy despite being used for years in high-risk groups.

Recent attempts to introduce new biomarker panels for ovarian cancer screening have faced regulatory challenges, leading to the withdrawal of two commercial tests due to concerns about their validation and effectiveness, highlighting the need for rigorous testing before public use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular signatures of ovarian cancer: from detection to prognosis. Walsh, CS., Karlan, BY.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7763876/

CA125 and Ovarian Cancer: A Comprehensive Review About 80% of patients with ovarian cancer exhibited elevated CA125 levels measured using this homologous double determinant assay, while only 1 ...

2. nature.com nature.com/articles/s41416-025-03165-4

CA125 and age-based models for ovarian cancer detection ... Cancer antigen-125 (CA125) is widely used to investigate symptoms of possible ovarian cancer (OC) in primary care.

3. emedicine.medscape.com emedicine.medscape.com/article/2087557-overview

CA 125: Reference Range, Interpretation, Collection and ... Cancer antigen 125 (CA 125) is the only tumor marker recommended for clinical use in the diagnosis and management of Ovarian Cancer.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5726402/

Early Detection of Ovarian Cancer using the Risk ... Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each ...

5. thelancet.com thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00590-5/fulltext

Estimating the ovarian cancer CA-125 preclinical ... The authors found 42 CA-125 samples in serous tumours and 153 CA-125 samples in non-serous tumours had level >35 U/ml, with an average time from ...

6. mayoclinic.org mayoclinic.org/diseases-conditions/ovarian-cancer/expert-answers/ca-125/faq-20058528

CA 125 test: A screening test for ovarian cancer? The cancer antigen 125 (CA 125) blood test generally isn't recommended if you have an average risk of ovarian cancer.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11346194/

The diagnostic performance of CA-125 for the detection ... CA-125 testing is a recommended first line investigation for women presenting with possible symptoms of ovarian cancer in English primary care.

8. nature.com nature.com/articles/s41598-024-71863-9

Automated early ovarian cancer detection system based on ... This article combines PET/CT imaging with serum CA125 detection to achieve automated early ovarian cancer detection by comprehensively analyzing ...