Cancer of Unknown Primary SiteCUP-COMPNCT04750109
Carcinoma of Unknown Primary (CUP): a Comparison Across Tissue and Liquid Biomarkers
An observational study of Cancer of Unknown Primary Site, run by The Christie NHS Foundation Trust at 7 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Cancer of Unknown Primary Site
- How many people
- 117 participants
- Where
- 7 sitesUnited Kingdom
- Study dates
- 9 Jun 2021to 28 Jun 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: All study participants must have a histological confirmed diagnosis of CUP based on the clinical, radiological and pathological review at a local or regional CUP MDT and the 2015 ESMO Clinical Practice Guidelines for CUP(Fizazi et al., 2015). Favourable and unfavourable-risk CUP subsets are eligible. The population to be included in this study corresponds to patients with CUP of epithelial origin for whom a likely tissue of origin cannot be determined.
Who may be able to join
- Aged 16 years or over
- Written informed consent according to ICH/GCP and national regulations
- ECOG Performance status 0-2
- Confirmed diagnosis of CUP as per the ESMO guidelines (described above). Patients must have;
- The local pathology reports confirming compatibility with CUP diagnosis and the associated slides used for the diagnosis
- Discussion at a local CUP MDT confirming diagnosis
Show all 9Show fewer
- Accessible tumour that can be safely biopsied using radiological techniques. Biopsy may be undertaken as standard of care (surplus tissue sample to be used for this protocol), or maximum of one fresh biopsy specifically for purposes of the protocol. Subjects with inaccessible tumours for biopsy specimens but with a confirmed CUP diagnosis, may be enrolled without a biopsy upon consultation and agreement by the sponsor
- Availability of archival tumour sample, slides and histological report
- Willingness to provide blood samples on up to three occasions during the course of the study
Who cannot join
- Patient with an immunohistochemistry profile that provides a definitive clinical indication of a primary cancer with a specific treatment
- Known HIV, Hepatitis B, C positive, or COVID-19 positive, due to the difficulties in handling high-risk specimens
- Patients who are unable to provide fully informed written consent
- Presence of any medical, psychological, familial or sociological condition that, in the investigator's opinion, will hamper compliance with the study protocol and follow-up schedule
- Bleeding diathesis (patients' on anticoagulation are permitted to enter the trial if anticoagulation can be safely managed to enable fresh tumour biopsies and blood sampling)
- Conditions in which research biopsies or blood sampling may increase risk of complications for the patients and/or investigator
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United Kingdom7 sites
Royal United Hospitals Bath NHS Foundation Trust
Bath, BA1 3NG
Velindre Cancer Centre
Cardiff, CF14 2TL
Edinburgh Cancer Centre
Edinburgh, EH4 2XR
UCL Cancer Institute
London, London, WC1E 6BT
The Christie NHS Foundation Trust
Manchester, M20 4BX
Clatterbridge Cancer Centre NHS Foundation Trust
Metropolitan Borough of Wirral, CH63 4JY
Torbay Hospital
Torquay, TQ2 7AA
About this study
Official title: Carcinoma of Unknown Primary (CUP): a Comparison Across Tissue and Liquid
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.
Read more
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.
- Conditions
- Cancer of Unknown Primary Site
- Medical subject headings
- Neoplasms, Unknown Primary
What is being measured
The primary outcome is the main question the study is designed to answer.
To sequence tumour tissue and circulating tumour DNA from approximately 120- 140 patients with CUP in order to evaluate the activation state of various oncogenic pathways and improve treatment stratification approaches
Measured: 18 months
To establish a genomic reporting mechanism whereby clinically relevant and potentially 'actionable' abnormalities found during sequencing/molecular characterisation can be reported to patients
Measured: 18 months
Secondary outcomes (8)
To obtain archival tumour specimens, fresh tissue and sequential blood samples from approximately 120 - 140 patients with CUP
Measured: 18 months
The comparative assessment of alternative assay methods (such as ctDNA) in parallel with whole genome sequencing in the diagnosis and treatment stratification for patients with CUP
Measured: 18 months
To collect samples for future analysis for additional molecular characterisation techniques for detection of actionable aberrations. Examples include RNA sequencing, IHC, proteomics, methylation, analysis of immuno-biomarkers
Measured: 18 months
To perform whole genome sequencing in patients where enough tumour tissue is available to explore novel predictive and resistance biomarkers
Measured: 18 months
To build on close collaborations between the NHS CUP Hospitals, and external collaborators to progress basic/translational research models to investigate biomarkers to treatment in CUP and key biological drivers of this disease.
Measured: 18 months
Collect evidence investigating the most effective way to stratify patients with CUP onto treatment.
Measured: 18 months
To understand whether liquid biomarkers in CUP can be used to stratify patients and give prognostic information
Measured: 18 months
Develop a data collection repository within the NHS for patients with CUP
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2021
- Study start9 Jun 2021
- Primary completion28 Jun 2024
- Study completion28 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancer of Unknown Primary SiteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Christie NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche, Concr, Durham University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04750109
- Sponsor's protocol ID
- CFTSp188
- Acronym
- CUP-COMP
- Status last verified
- Jul 2024
- First submitted
- 10 Feb 2021
- Last updated
- 10 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Carcinoma of Unknown Primary (CUP): a Comparison Across Tissue and Liquid
- ClinicalTrials.gov ID
- NCT04750109
- Acronym / sponsor ID
- CUP-COMP / CFTSp188
- Conditions
- Cancer of Unknown Primary Site
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 117 participants (actual)
- Lead sponsor
- The Christie NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche, Concr, Durham University
- Study start
- 9 Jun 2021 (actual)
- Primary completion
- 28 Jun 2024 (actual)
- Study completion
- 28 Jun 2024 (actual)
- First posted
- 11 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- All study participants must have a histological confirmed diagnosis of CUP based on the clinical, radiological and pathological review at a local or regional CUP MDT and the 2015 ESMO Clinical Practice Guidelines for CUP(Fizazi et al., 2015). Favourable and unfavourable-risk CUP subsets are eligible. The population to be included in this study corresponds to patients with CUP of epithelial origin for whom a likely tissue of origin cannot be determined.
Key inclusion criteria (9 listed)
- Aged 16 years or over
- Written informed consent according to ICH/GCP and national regulations
- ECOG Performance status 0-2
- Confirmed diagnosis of CUP as per the ESMO guidelines (described above). Patients must have;
- Accessible tumour that can be safely biopsied using radiological techniques. Biopsy may be undertaken as standard of care (surplus tissue sample to be used for this protocol), or maximum of one fresh biopsy specifically for purposes of the protocol. Subjects with inaccessible tumours for biopsy specimens but with a confirmed CUP diagnosis, may be enrolled without a biopsy upon consultation and agreement by the sponsor
Key exclusion criteria (6 listed)
- Patient with an immunohistochemistry profile that provides a definitive clinical indication of a primary cancer with a specific treatment
- Known HIV, Hepatitis B, C positive, or COVID-19 positive, due to the difficulties in handling high-risk specimens
- Patients who are unable to provide fully informed written consent
- Presence of any medical, psychological, familial or sociological condition that, in the investigator's opinion, will hamper compliance with the study protocol and follow-up schedule
- Bleeding diathesis (patients' on anticoagulation are permitted to enter the trial if anticoagulation can be safely managed to enable fresh tumour biopsies and blood sampling)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To sequence tumour tissue and circulating tumour DNA from approximately 120- 140 patients with CUP in order to evaluate the activation state of various oncogenic pathways and improve treatment stratification approaches
Time frame: 18 months
To establish a genomic reporting mechanism whereby clinically relevant and potentially 'actionable' abnormalities found during sequencing/molecular characterisation can be reported to patients
Time frame: 18 months
8 secondary outcomes
To obtain archival tumour specimens, fresh tissue and sequential blood samples from approximately 120 - 140 patients with CUP
Time frame: 18 months
The comparative assessment of alternative assay methods (such as ctDNA) in parallel with whole genome sequencing in the diagnosis and treatment stratification for patients with CUP
Time frame: 18 months
To collect samples for future analysis for additional molecular characterisation techniques for detection of actionable aberrations. Examples include RNA sequencing, IHC, proteomics, methylation, analysis of immuno-biomarkers
Time frame: 18 months
To perform whole genome sequencing in patients where enough tumour tissue is available to explore novel predictive and resistance biomarkers
Time frame: 18 months
To build on close collaborations between the NHS CUP Hospitals, and external collaborators to progress basic/translational research models to investigate biomarkers to treatment in CUP and key biological drivers of this disease.
Time frame: 18 months
Collect evidence investigating the most effective way to stratify patients with CUP onto treatment.
Time frame: 18 months
To understand whether liquid biomarkers in CUP can be used to stratify patients and give prognostic information
Time frame: 18 months
Develop a data collection repository within the NHS for patients with CUP
Time frame: 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cancer of Unknown Primary Site, run by The Christie NHS Foundation Trust at 7 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To sequence tumour tissue and circulating tumour DNA from approximately 120- 140 patients with CUP in order to evaluate the activation state of various oncogenic pathways and improve treatment stratification approaches (time frame: 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2024.