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

Trial Summary

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 data supports the effectiveness of this treatment for early detection of ovarian cancer?

Monitoring CA-125 levels over time can help detect ovarian cancer early, as it has shown a high specificity of 99.6% when used in serial measurements. However, its sensitivity is limited, and it may not detect all early-stage cancers, so it is most effective when combined with other screening methods. ^{1 2 3 4 5}

Is the CA 125 blood test safe for humans?

The CA 125 blood test is generally considered safe for humans, but it is not recommended for routine screening of ovarian cancer due to potential harms and lack of evidence for effectiveness. ^{6 7 8 9 10}

How does the CA 125 blood test differ from other treatments for ovarian cancer?

The CA 125 blood test is unique because it is not a treatment but a diagnostic tool used to detect ovarian cancer by measuring the level of a specific protein in the blood. Unlike treatments that aim to cure or manage the disease, this test helps in early detection, although it is not always reliable for all women, especially those with early-stage cancer or certain subtypes. ^{11 12 13 14 15}

What is the purpose of this trial?

The goal of this clinical research study is to evaluate a method involving 4 blood tests called CA-125, HE4, HE4 antigen autoantibody complexes, and osteopontin that may be helpful in the early detection of ovarian cancer in women who are at low risk.

Research Team

Denise Nebgen, MD, PHD

Principal Investigator

The University of Texas MD Anderson Cancer Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. Greece pubmed.ncbi.nlm.nih.gov

CA-125 monitoring in the management of ovarian cancer. [2004]

2. United States pubmed.ncbi.nlm.nih.gov

The effectiveness of ovarian cancer screening. A decision analysis model. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

Preoperative CA 125 levels: an independent prognostic factor for epithelial ovarian cancer. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Molecular signatures of ovarian cancer: from detection to prognosis. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Development and validation of circulating CA125 prediction models in postmenopausal women. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Use of CA-125 Tests and Computed Tomographic Scans for Surveillance in Ovarian Cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

CA 125 as a screening test for ovarian cancer. [2017]

11. United States 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. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Multiple biomarker panels for early detection of ovarian cancer. [2015]

13. United States pubmed.ncbi.nlm.nih.gov

The role of CA 125 in screening for ovarian cancer. [2022]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Salvaging Detection of Early-Stage Ovarian Malignancies When CA125 Is Not Informative. [2021]

15. England 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. [2021]