Transvaginal Ultrasound Screening for Ovarian Cancer

Overseen By Edward J Pavlik, PhD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: John R van Nagell

Disqualifiers: Pelvic symptoms, Pelvic mass, Pregnancy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

65000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether regular transvaginal ultrasounds (a type of internal imaging) can detect ovarian cancer earlier and more accurately in women at higher risk. The goal is to reduce false alarms and improve the chances of detecting cancer if present. Women in Kentucky who might be suitable include those over 50, those with a family history of ovarian cancer, or those who have had breast cancer. Participants will receive ongoing screenings as long as they choose to remain in the study. As an unphased trial, this study offers participants the opportunity to contribute to important research that could lead to earlier detection of ovarian cancer.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that transvaginal ultrasonography is safe for ovarian cancer screening?

Research has shown that transvaginal ultrasound is generally safe and well-tolerated. This method uses sound waves to create images of the ovaries, aiding in the detection of ovarian cancer. It is non-invasive and does not involve radiation, reducing potential risks.

Studies have not identified significant harmful effects from this type of screening. It has been used successfully in many women, demonstrating benefits such as improved survival rates for those whose cancers are detected through screening. However, like any screening, it can produce false positives or negatives. A false positive indicates cancer when none is present, while a false negative misses existing cancer.

Overall, the safety record for transvaginal ultrasound remains positive, making it a promising option for ovarian cancer screening. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about serial transvaginal ultrasonography (TVS) for ovarian cancer screening because it offers a non-invasive and potentially more accurate way to detect ovarian cancer early. Unlike traditional methods like CA-125 blood tests or pelvic exams, which can have limitations in early detection, TVS uses detailed imaging to visualize the ovaries directly. This method could lead to earlier and more reliable diagnosis, improving outcomes for patients by catching cancer at a more treatable stage.

What evidence suggests that serial transvaginal ultrasonography is effective for ovarian cancer screening?

Research has shown that transvaginal ultrasound (TVS) effectively identifies ovarian issues, aiding in the detection of possible ovarian cancer. Studies have found that women whose ovarian cancer was detected through TVS screening have a long-term survival rate twice as high as those who were not screened (65% vs. 32%). Participants in this trial will undergo serial transvaginal ultrasonography (TVS) screening as part of the Kentucky Ovarian Cancer Screening Program. TVS screening is associated with detecting ovarian cancer at an earlier stage, which can lead to lower mortality rates. While TVS effectively identifies changes in the ovaries, it is less reliable in determining if these changes are cancerous. However, regular screenings increase the chance of accurately detecting cancer, offering hope to those at risk. ^{1 3 5 6 7}

Who Is on the Research Team?

John R Van Nagell, MD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for women over 50, or those with a family history of ovarian cancer over 24 years old, and women over 24 with a personal history of breast cancer. Participants must have at least one ovary, be able to consent, and have an ECOG performance status up to 2.34. It excludes symptomatic individuals, prisoners, pregnant women, those unable to understand the study or give informed consent.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

I am a woman aged over 50 years.

I have had a hysterectomy but still have at least one ovary.

Exclusion Criteria

I have had ovarian cancer in the past.

Exclusions will apply to anyone who presents with factors or issues that prevent them from understanding the screening research procedures or completing the informed consent component or personal information needed for the study

You cannot have a transvaginal ultrasound because of issues with vaginal size, infections, or difficulty placing your body in the right position for the test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Serial Transvaginal Ultrasonography

Participants undergo serial transvaginal ultrasonography (TVS) screening to detect ovarian cancer

3 years

Regular visits as per screening protocol

Follow-up

Participants are monitored for safety and effectiveness after screening

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Serial Transvaginal Ultrasonography

Trial Overview The study tests if serial transvaginal ultrasonography can effectively screen for ovarian cancer in high-risk women by reducing false positives and increasing positive predictive value without missing true cases or creating false negatives. Women will receive ongoing screening based on a specific algorithm.

How Is the Trial Designed?

Group I: Participants in the Kentucky Ovarian Cancer Screening Program Experimental Treatment 1 Intervention

Participants from the Kentucky Ovarian Cancer Screening Program who choose to participate in this trial will undergo further serial transvaginal ultrasonography (TVS) screening.

Serial Transvaginal Ultrasonography is already approved in United States, European Union for the following indications:

Approved in United States as Transvaginal Ultrasonography for:

• Screening for ovarian cancer in intermediate to high-risk women

Approved in European Union as Transvaginal Ultrasonography for:

• Diagnostic imaging for ovarian abnormalities

Who Is Running the Clinical Trial?

John R van Nagell

Lead Sponsor

Trials

1

Recruited

65,000+

Published Research Related to This Trial

In a study involving 43,867 postmenopausal women from the UKCTOCS trial, factors such as previous hysterectomy, age, and obesity significantly decreased the likelihood of visualizing ovaries during transvaginal sonography (TVS).

Conversely, a history of infertility and older age at menopause were associated with better ovarian visualization, highlighting the importance of these factors in ovarian cancer screening strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors affecting visualization of postmenopausal ovaries: descriptive study from the multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Sharma, A., Burnell, M., Gentry-Maharaj, A., et al.[2022]

The combination of serum CA125 levels exceeding 30 U/ml and a Transvaginal Ultrasound (TVUS) score of 35 or higher demonstrated a high sensitivity of 81.7% and perfect specificity of 100% for predicting ovarian cancer in a study of 120 women.

This study suggests that using both CA125 and TVUS together can provide a reliable method for screening ovarian cancer, but further research with a larger population is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum CA 125 combined with transvaginal ultrasonography for ovarian cancer screening. Roupa, Z., Faros, E., Raftopoulos, V., et al.[2019]

Annual transvaginal sonography (TVS) screening in 14,469 asymptomatic women significantly improved the early detection of ovarian cancer, with 17 cancers identified, mostly at earlier stages (Stage I and II), leading to high survival rates of 95% at 2 years for screened patients.

While TVS screening showed high sensitivity (81%) and specificity (98.9%), it was less effective in detecting cancers when ovarian volume was normal, indicating that normal scans do not guarantee the absence of disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of transvaginal sonographic screening in asymptomatic women at risk for ovarian cancer. van Nagell, JR., DePriest, PD., Reedy, MB., et al.[2016]

Annual transvaginal sonography (TVS) screening in over 25,000 women showed a high sensitivity (85.0%) and specificity (98.7%) for detecting ovarian cancer, leading to earlier stage detection and improved survival rates for patients diagnosed through screening.

Despite its effectiveness, TVS screening had limitations, including false-negative results where some women developed ovarian cancer within 12 months of a negative screen, highlighting the need for continued monitoring even after normal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovarian cancer screening with annual transvaginal sonography: findings of 25,000 women screened. van Nagell, JR., DePriest, PD., Ueland, FR., et al.[2022]

Transvaginal sonography (TVS) was effective in screening 1300 asymptomatic postmenopausal women for ovarian abnormalities, detecting issues in 2.5% of participants, including two cases of Stage I ovarian carcinoma.

Both women diagnosed with ovarian cancer had normal pelvic exams and CA-125 levels, highlighting the importance of TVS as a reliable screening tool, as there have been no deaths from ovarian cancer in over 3000 patient years of follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovarian cancer screening in asymptomatic postmenopausal women by transvaginal sonography. Van Nagell, JR., DePriest, PD., Puls, LE., et al.[2019]

In a study involving 3220 asymptomatic postmenopausal women screened with transvaginal sonography (TVS), the method successfully identified ovarian abnormalities, leading to the detection of three cases of early-stage ovarian cancer, all of whom are alive after treatment.

The screening demonstrated a reduction in the stage at which ovarian cancer was detected and has not resulted in any ovarian cancer deaths among the screened population, suggesting that TVS could be an effective screening tool for early detection of ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovarian cancer screening in asymptomatic postmenopausal women. DePriest, PD., van Nagell, JR., Gallion, HH., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3873201/

Transvaginal ultrasonography in ovarian cancer screening TVS is accurate in detecting abnormalities in ovarian volume and morphology, but is less reliable in differentiating benign from malignant ovarian tumors.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04473833

Transvaginal Ultrasonography As a Screening Method for ... The long-term survival (20 year) of women with screen-detected ovarian cancers is twice that of unscreened women (65% vs 32%). Separation of cases into Type 1 ...

3. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.22594

Ovarian cancer screening with annual transvaginal sonography TVS screening, when it was performed annually, was associated with a decrease in disease stage at detection and with case-specific ovarian cancer mortality.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825800958165

The Efficacy of Transvaginal Sonographic Screening in ... After 46,113 screening years, there have been 3 ovarian cancer deaths in the annually screened population and 2 ovarian cancer deaths in women receiving less ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02424

Compelling Story of Ovarian Cancer Screening The two-stage screening approach using serial CA125 and TVS performed exceedingly well, even considering that not all ovarian cancers express CA125.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5788737/

Screening for ovarian cancer: imaging challenges and ... In the PLCO trial, 85% of screen-detected ovarian cancers with negative TVU screens were detected in late stage III/IV and 54% of fatal screen-detected cases ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3991859/

Ovarian cancer screening—Current status, future directions During prevalence screening, both MMS and USS strategies had encouraging sensitivity for primary invasive epithelial ovarian/tubal cancers (89.5% and 75%, ...