CUP-COMP
Research type
Research Study
Full title
Carcinoma of Unknown Primary Site (CUP):A comparison across tissue and liquid biomarkers (CUP-COMP)
IRAS ID
284749
Contact name
Natalie Cook
Contact email
Sponsor organisation
The Christie NHS Foundation Trust
Duration of Study in the UK
1 years, 2 months, 31 days
Research summary
Research Summary:
Patients with Carcinoma of Unknown Primary (CUP) have widespread cancer at diagnosis however the specific site of origin cannot be found, despite significant testing, making it difficult to treat. CUP has a poor prognosis; it is the 6th most common cause of cancer death in the UK.
To date there have been limited studies investigating molecular genomics in CUP patients, resulting in limited evidence to evaluate whether genomic profiling has added value over and above the standard diagnostics provided in the NHS.
As a result, our project will aim to;
• Assess genomic sequencing (both in tissue and blood) for the diagnosis and treatment guidance in CUP patients including a comparison of the effectiveness of tissue and blood based biomarkers
• Collect evidence to further develop technology that predicts an individual's response to a treatment
• Develop innovative systems of clinical data capture in patients with CUP
• Investigate novel biomarkers to determine the primary tumour location
Approximately 120-140 CUP patients will be recruited across 7 UK NHS sites. Tumour samples will be collected from patients undergoing a standard of care procedure OR medically fit patients with accessible tumour. Archival tumour may also be obtained. Some samples will be stored for future translational research.
Sequencing results alongside clinical data will be discussed by a multi-disciplinary CUP Molecular Tumour Board. They will provide oversight on the nature, clinical significance and relevance of the results. They will inform the local CUP team of any “actionable” genetic changes, which could potentially direct selection of a targeted therapy trial for that patient. Sequential blood samples will be collected to investigate genetic characteristics that may be able to predict response to therapy.
The aggregated anonymised data will be made publicly available following completion of this trial.Summary of Results:
The Carcinoma of Unknown Primary (CUP): A comparison across tissue and liquid biomarkers study (CUP-COMP; IRAS 284749; NCT04750109). CUP-COMP was an industry-led collaborative project funded by Innovate UK. The sponsor of this study was The Christie NHS Foundation Trust. This was a basic science study involving human participants.
CUP-COMP compared blood and tissue-based testing interventions in patients diagnosed with CUP. It was set up at 7 sites across England, Wales and Scotland. Between June 2021 and February 2023 CUP-COMP recruited 117 patients diagnosed with CUP. 66 (56%) were female and 51 (44%) were male. The mean age of participants was 63 years, and the study recruited patients with both ‘favourable’ and ‘poor-risk’ CUP subtypes.
At baseline, participants had a blood-based "liquid-biopsy" test. Where possible participants also had fresh tumour biopsy for whole genome sequencing and archival tissue samples were tested where fresh tissue was not collected. On disease progression and where possible, participants had a repeat blood-based test. All test results were discussed with the support of experts from the North-West Genomics Laboratory Hub (GLH). Any change to patient care was the decision of the clinical team and not trial mandated.
Most participants had at least one blood sample collected and tested. Fresh tissue biopsies were not practical for most patient. Even access to archival tissue that met the testing requirements was difficult. The relative ease of blood-based diagnostic testing in CUP is of critical importance. CUP-COMP showed that blood-based diagnostic testing was beneficial in certain cases. A full publication with detailed results from the CUP-COMP study is being developed. The publication will further detail how disease presentation impacts blood-based testing. The findings also support similar studies that suggest blood-based testing could improve the diagnostic pathway.
Access to diagnostic tests vary between England, Scotland and Wales. Further trials to improve the diagnostic pathway could reduce regional inequalities of care. To this end, we have setup the EGG-CUP study (REC: 24/NW/0181). EGG-CUP is currently recruiting patients diagnosed with CUP in the Northwest of England.
The CUP-COMP team would like to thank again all the patients involved.
REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
20/YH/0305
Date of REC Opinion
23 Nov 2020
REC opinion
Further Information Favourable Opinion