CA125 and Ultrasound in Detecting Ovarian Cancer in Postmenopausal Women (UKCTOCS)

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ClinicalTrials.gov Identifier: NCT00058032

Recruitment Status : Completed

First Posted : April 9, 2003

Last Update Posted : November 19, 2020

Sponsor:

Collaborators:

National Institute for Health Research, United Kingdom

The Eve Appeal

Medical Research Council

Cancer Research UK

Information provided by (Responsible Party):

University College, London

Study Description

Brief Summary:

RATIONALE: Screening tests may help doctors detect ovarian cancer early when the survival is much more encouraging. It is not yet known whether a CA125-based or ultrasound strategy is more effective in detecting ovarian cancer early thereby impacting on the mortality from the disease in postmenopausal women from the general population.

PURPOSE: Randomized clinical trial to assess the impact of screening using a multimodal strategy using CA125 interpreted by the Risk of Ovarian Cancer Algorithm (ROCA) followed by transvaginal ultrasound as a second line test versus transvaginal ultrasound on mortality from the disease in postmenopausal women from the general population.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer	Other: screening questionnaire administration Procedure: annual screening	Not Applicable

Detailed Description:

OBJECTIVES:

Determine the impact of preclinical detection of ovarian cancer by screening on ovarian cancer mortality in postmenopausal women.
Determine the physical morbidity of ovarian cancer screening in this population.
Determine the psychological consequences of screening results (true negative, true positive, false negative, and false positive) in this population.
Compare the interventions that result from screening for ovarian cancer using CA 125 monitoring and ultrasound in this population.
Compare the feasibility of population screening, in terms of compliance rates with annual screening for ovarian cancer with these strategies.
Compare the performance of these screening strategies in this population.

OUTLINE: This is a randomized, multicenter study. Participants are randomized to 1 of 3 screening arms.

Arm I: Participants do not undergo screening.
Arm II: Participants undergo screening with an annual CA 125 level interpreted using the Risk of Ovarian Cancer Algorithm (ROCA). Depending on the results of the test, some patients may undergo additional screening.
Arm III: Participants undergo screening with an annual transvaginal or transabdominal ultrasound. Depending on the results of the test, some patients may undergo additional screening.

Participants in all arms complete a health questionnaire at 3-5 years after study entry and in 2014.

PROJECTED ACCRUAL: A total of 200,000 participants (100,000 for arm I and 50,000 each for arms II and III) will be accrued for this study within 5 years.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	202638 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	202,638 participants randomised to: Multimodal Group: 50640 Ultrasound Group: 50639 Control Group: 101359
Masking:	None (Open Label)
Primary Purpose:	Screening
Official Title:	United Kingdom Collaborative Trial Of Ovarian Cancer Screening
Actual Study Start Date :	April 17, 2001
Actual Primary Completion Date :	September 29, 2005
Actual Study Completion Date :	June 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Ovarian cancer

MedlinePlus related topics: Ovarian Cancer

Genetic and Rare Diseases Information Center resources: Ovarian Cancer Ovarian Epithelial Cancer

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

UKCTOCS (2001-2014): Death due to ovarian cancer (WHO 2003) determined by independent outcomes committee review of patient notes for all women identified to have a 'possible ovarian cancer' (pre-specified ICD-10 codes) till 31st December 2014.
Long term impact of screening on ovarian cancer mortality in the UKCTOCS (LTFU UKCTOCS) (2015-2021): Death due to ovarian cancer (WHO 2014) determined by independent outcomes committee review till 30 June 2020.

Secondary Outcome Measures :

Performance characteristics: Sensitivity, specificity, positive predictive values of the two screening strategies (multimodal and ultrasound) for detection of ovarian cancer diagnosed within one year of last screen.
Ovarian cancer diagnosis is based on outcomes review of medical notes of all women who developed ovarian cancer during the trial.
Surgical complications in women who underwent false positive surgery and were found to have benign or normal adnexae.
This is assessed through central medical note review and assigned by designated trial gynaecological oncologist.
Cost-effectivenesss of the multimodal (MMS) and ultrasound screening (USS) strategies separately comparing them to a no-screening arm.
Cost-effectivenesss of the multimodal (MMS) and ultrasound screening (USS) strategies separately comparing them to a no-screening arm: (a) Incremental cost-effectiveness analysis over the 14 year period of the trial (censorship 31st Dec 2014); (b) Incremental cost-effectiveness analysis for the cumulative mortality estimated over a 25-year period by extrapolating beyond the 14 years of the trial
Compliance with annual screening: The proportion of women who attended all tests that formed part of an annual screening episode of the total who were eligible for that annual screening episode.
Psychological morbidity related to screening - assessed in a separate MRC funded study, UKCTOCS Psychosocial study, PI Prof Dame Lesley Fallowfield.

Eligibility Criteria

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Ages Eligible for Study:	50 Years to 74 Years (Adult, Older Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

DISEASE CHARACTERISTICS:

Postmenopausal, as defined by meeting 1 of the following criteria:
- More than 12 months of amenorrhea after natural menopause or hysterectomy
- Received more than 12 months of hormone replacement therapy for menopausal symptoms
No prior ovarian malignancy
No prior bilateral oophorectomy
Not at high risk for ovarian cancer due to familial predisposition as defined by the UKCCCR Familial Ovarian Cancer Screening Study

PATIENT CHARACTERISTICS:

Age

50 to 74

Performance status

Not specified

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Not specified

Renal

Not specified

Other

No active non-ovarian malignancy
- Prior malignancy allowed provided there is no documented persistent or recurrent disease and patient has not received treatment for more than 1 year

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

See Disease Characteristics

Radiotherapy

Not specified

Surgery

See Disease Characteristics

Other

No concurrent participation in any other ovarian cancer screening study

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00058032

Sponsors and Collaborators

University College, London

National Institute for Health Research, United Kingdom

The Eve Appeal

Medical Research Council

Cancer Research UK

Investigators

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Principal Investigator:	Usha Menon, MBBS, MRCOG	University College, London

More Information

Publications of Results:

Jacobs I, Gentry-Maharaj A, Burnell M, Manchanda R, Singh N, Sharma A, Ryan A, Seif MW, Amso NN, Turner G, Brunell C, Fletcher G, Rangar R, Ford K, Godfrey K, Lopes A, Oram D, Herod J, Williamson K, Scott I, Jenkins H, Mould T, Woolas R, Murdoch J, Dobbs S, Leeson S, Cruickshank D, Skates SJ, Fallowfield L, Parmar M, Campbell S, Menon U. Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal women: a case-control study within the UKCTOCS cohort. Lancet Oncol. 2011 Jan;12(1):38-48. doi: 10.1016/S1470-2045(10)70268-0. Epub 2010 Dec 10.

Menon U, Gentry-Maharaj A, Hallett R, Ryan A, Burnell M, Sharma A, Lewis S, Davies S, Philpott S, Lopes A, Godfrey K, Oram D, Herod J, Williamson K, Seif MW, Scott I, Mould T, Woolas R, Murdoch J, Dobbs S, Amso NN, Leeson S, Cruickshank D, McGuire A, Campbell S, Fallowfield L, Singh N, Dawnay A, Skates SJ, Parmar M, Jacobs I. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol. 2009 Apr;10(4):327-40. doi: 10.1016/S1470-2045(09)70026-9. Epub 2009 Mar 11.

Jacobs IJ, Menon U, Ryan A, Gentry-Maharaj A, Burnell M, Kalsi JK, Amso NN, Apostolidou S, Benjamin E, Cruickshank D, Crump DN, Davies SK, Dawnay A, Dobbs S, Fletcher G, Ford J, Godfrey K, Gunu R, Habib M, Hallett R, Herod J, Jenkins H, Karpinskyj C, Leeson S, Lewis SJ, Liston WR, Lopes A, Mould T, Murdoch J, Oram D, Rabideau DJ, Reynolds K, Scott I, Seif MW, Sharma A, Singh N, Taylor J, Warburton F, Widschwendter M, Williamson K, Woolas R, Fallowfield L, McGuire AJ, Campbell S, Parmar M, Skates SJ. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2016 Mar 5;387(10022):945-956. doi: 10.1016/S0140-6736(15)01224-6. Epub 2015 Dec 17. Erratum in: Lancet. 2016 Mar 5;387(10022):944. Erratum in: Lancet. 2016 Mar 5;387(10022):944.

Menon U, Ryan A, Kalsi J, Gentry-Maharaj A, Dawnay A, Habib M, Apostolidou S, Singh N, Benjamin E, Burnell M, Davies S, Sharma A, Gunu R, Godfrey K, Lopes A, Oram D, Herod J, Williamson K, Seif MW, Jenkins H, Mould T, Woolas R, Murdoch JB, Dobbs S, Amso NN, Leeson S, Cruickshank D, Scott I, Fallowfield L, Widschwendter M, Reynolds K, McGuire A, Campbell S, Parmar M, Skates SJ, Jacobs I. Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening. J Clin Oncol. 2015 Jun 20;33(18):2062-71. doi: 10.1200/JCO.2014.59.4945. Epub 2015 May 11.

Menon U, Gentry-Maharaj A, Ryan A, Sharma A, Burnell M, Hallett R, Lewis S, Lopez A, Godfrey K, Oram D, Herod J, Williamson K, Seif M, Scott I, Mould T, Woolas R, Murdoch J, Dobbs S, Amso N, Leeson S, Cruickshank D, McGuire A, Campbell S, Fallowfield L, Skates S, Parmar M, Jacobs I. Recruitment to multicentre trials--lessons from UKCTOCS: descriptive study. BMJ. 2008 Nov 13;337:a2079. doi: 10.1136/bmj.a2079. Erratum in: BMJ. 2008;337:a2976.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Menon U, Gentry-Maharaj A, Burnell M, Singh N, Ryan A, Karpinskyj C, Carlino G, Taylor J, Massingham SK, Raikou M, Kalsi JK, Woolas R, Manchanda R, Arora R, Casey L, Dawnay A, Dobbs S, Leeson S, Mould T, Seif MW, Sharma A, Williamson K, Liu Y, Fallowfield L, McGuire AJ, Campbell S, Skates SJ, Jacobs IJ, Parmar M. Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2021 Jun 5;397(10290):2182-2193. doi: 10.1016/S0140-6736(21)00731-5. Epub 2021 May 12.

Russell MR, Graham C, D'Amato A, Gentry-Maharaj A, Ryan A, Kalsi JK, Whetton AD, Menon U, Jacobs I, Graham RLJ. Diagnosis of epithelial ovarian cancer using a combined protein biomarker panel. Br J Cancer. 2019 Sep;121(6):483-489. doi: 10.1038/s41416-019-0544-0. Epub 2019 Aug 7.

Fraser L, Burnell M, Salter LC, Fourkala EO, Kalsi J, Ryan A, Gessler S, Gidron Y, Steptoe A, Menon U. Identifying hopelessness in population research: a validation study of two brief measures of hopelessness. BMJ Open. 2014 May 30;4(5):e005093. doi: 10.1136/bmjopen-2014-005093.

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Responsible Party:	University College, London
ClinicalTrials.gov Identifier:	NCT00058032
Other Study ID Numbers:	CDR0000285690 UKCTOCS EU-20249
First Posted:	April 9, 2003 Key Record Dates
Last Update Posted:	November 19, 2020
Last Verified:	November 2020

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by University College, London:


ovarian epithelial cancer

Additional relevant MeSH terms:

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Ovarian Neoplasms Carcinoma, Ovarian Epithelial Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases	Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type

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