Clinical trial NCT00058032: CA125 and Ultrasound in Detecting Ovarian Cancer in Postmenopausal Women
Official title: United Kingdom Collaborative Trial Of Ovarian Cancer Screening
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ovarian Cancer
Keywords: ovarian epithelial cancer
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
name: The Eve Appeal
name: Medical Research Council
name: Cancer Research UK
First posted: 2003-04-09
Enrollment: 202638
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 202,638 participants randomised to: Multimodal Group: 50640 Ultrasound Group: 50639 Control Group: 101359
Primary purpose: SCREENING

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.

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.

Eligibility 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

Primary outcomes:
measure: 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.
measure: 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 outcomes:
measure: 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.
measure: Surgical complications in women who underwent false positive surgery and were found to have benign or normal adnexae.
measure: Cost-effectivenesss of the multimodal (MMS) and ultrasound screening (USS) strategies separately comparing them to a no-screening arm.
measure: 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.
measure: Psychological morbidity related to screening - assessed in a separate MRC funded study, UKCTOCS Psychosocial study, PI Prof Dame Lesley Fallowfield.
Other outcomes:
Locations:
Study officials:
affiliation: University College, London
name: Usha Menon, MBBS, MRCOG
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.