Clinical trial NCT06129968: Transforming Ovarian Cancer Diagnostic Pathways
Official title: Transforming Ovarian Cancer Diagnostic Pathways (TranSforming Ovarian caNcer diAgnosTic pAthways: A Hybrid Type 1 Effectiveness-implementation Study of a Novel Biomarker Based, Threshold Driven Pathway for Earlier Ovarian Cancer Diagnosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ovarian Cancer
Keywords: ovarian cancer
diagnosis
Primary care
CA125
HE4
ROMA algorithm
Lead sponsor: Sandwell & West Birmingham Hospitals NHS Trust
Sponsor class: OTHER
Collaborators: name: University of Birmingham
First posted: 2023-11-13
Enrollment: 34000
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: * Women presenting to primary care with suspected ovarian cancer who are tested for the biomarker CA125 according to current standards of care for investigation of CA125 in the primary care setting.
* All samples requested by GPs for testing with CA125 in women in two large labs, Black Country Pathology Wervices and South Tyne and Wear labs, will be included.

Brief summary: The goal of this observational cohort study is to compare the diagnostic accuracy and cost effectiveness of Risk of Malignancy Algorithm (ROMA) compared with CA125 in the diagnosis of ovarian cancer in patients attending their general practitioner (GP) with symptoms that sometimes might indicate ovarian cancer. The main questions it aims to answer are: • what is the accuracy of the ROMA algorithm which uses the blood tests CA125 and Human epididymis protein 4 (HE4) compared to CA125 in diagnosing ovarian cancer, particularly early-stage ovarian cancer, in women tested for suspected ovarian cancer from primary care? • What is the cost-effectiveness of ROMA versus CA125 testing in primary care to diagnose ovarian cancer? When a participant's GP orders a CA125 blood test, the blood will also be tested for HE4 and the ROMA algorithm calculated. The diagnostic accuracy of ROMA and CA125 will be compared to see if ROMA would be a better diagnostic test for ovarian cancer when used in the primary care setting.

Detailed description: A woman's chances of surviving 5 years after Ovarian Cancer (OC) diagnosis drops from 90% if diagnosed at Stage 1 to 15% at Stage 4. Currently, GPs use a blood test called CA125 and ultrasound scan to decide whether to refer a woman to hospital for suspected OC. CA125 misses 50% of early-stage cancers (Stage 1 and 2); both tests cause unnecessary referrals. Recently, a blood test called Human epididymis protein 4 (HE4) in combination with CA125 in a formula called ROMA (Risk of Malignancy Algorithm) has been developed. ROMA is used by doctors in the US and Europe to guide referrals and recommended by the American College of Obstetrics and Gynaecology. A large Cochrane systematic review of 30,000+ patients across 50 papers shows ROMA detects more cancers at earlier stage than a combination of CA125 and ultrasound. All included studies were conducted in hospital where OC rates are high, however a model at 3% OC rate shows that ROMA is superior. Before the test can be introduced in NHS, it is necessary to confirm this evidence in a large primary care study and establish cost effectiveness. The wider NHS cancer programme funded SONATA project evaluates an integrated pathway from community to cancer specialists using ROMA. It includes National Health Service (NHS) pilots in primary and secondary care to establish how practice can be supported to change, evaluates facilitators and barriers to change as well as a community campaign to promote OC awareness. This study is one component of the SONATA project. In it, two large NHS labs will additionally test 41,000 blood samples from women whose GPs requested CA125 testing for suspected OC with ROMA to accurately identify the number of patients who can be detected earlier. This will enable the investigators to establish cost effectiveness of ROMA and definitive data on accuracy in primary care.

Eligibility criteria: Inclusion Criteria:

* Women presenting to primary care with suspected ovarian cancer who are tested for the biomarker CA125 according to current standards of care for investigation of CA125 in the primary care setting.

Exclusion Criteria:

* Patients presenting to primary care who do not have potential symptoms of ovarian cancer.
* Women with symptoms sometimes associated with ovarian cancer not tested for ovarian cancer.

Primary outcomes:
measure: Sensitivity of ROMA versus CA125 in early stage ovarian cancer
timeFrame: 12 months
measure: Specificity of ROMA versus CA125 in early stage ovarian cancer
timeFrame: 12 months
Secondary outcomes:
measure: Sensitivity of ROMA versus CA125 in all stages of ovarian cancer
timeFrame: 12 months
measure: Specificity of ROMA versus CA125 in all stages of ovarian cancer
timeFrame: 12 months
measure: Incremental Cost Effectiveness Ratio (ICER) of ROMA versus CA125
timeFrame: 12 months
Other outcomes:
measure: Number of health care visits
timeFrame: 12 months
measure: Rate of Emergency Hospital admissions
timeFrame: 12 months
measure: Cancer stage
timeFrame: 12 months
measure: % of each treatment modality (surgical resection and chemotherapy, chemotherapy alone, surgical resection alone, or other)
timeFrame: 12 months
measure: Survival
timeFrame: 12 months
Locations:
city: Birmingham
country: United Kingdom
facility: Sandwell and West Birmingham NHS TRUST
city: Gateshead
country: United Kingdom
facility: Gateshead Health NHS Foundation Trust
city: Wolverhampton
country: United Kingdom
facility: The Royal Wolverhampton NHS Trust
Study officials:
affiliation: University of Birmingham/Sandwell and West Birmingham NHS Trust
name: Sudha Sundar
role: PRINCIPAL_INVESTIGATOR
References: