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Carcinoma of Unknown Primary (CUP): A Comparison Across Tissue and Liquid Biomarkers (CUP-COMP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04750109
Recruitment Status : Recruiting
First Posted : February 11, 2021
Last Update Posted : August 6, 2021
Sponsor:
Collaborators:
Hoffmann-La Roche
ConcR
Durham University
Information provided by (Responsible Party):
The Christie NHS Foundation Trust

Brief 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.


Condition or disease
Cancer of Unknown Primary Site

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Study Type : Observational
Estimated Enrollment : 140 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Carcinoma of Unknown Primary (CUP): A Comparison Across Tissue and Liquid
Actual Study Start Date : June 9, 2021
Estimated Primary Completion Date : March 30, 2022
Estimated Study Completion Date : March 30, 2022



Primary Outcome Measures :
  1. 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 ]
  2. 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 ]

Secondary Outcome Measures :
  1. To obtain archival tumour specimens, fresh tissue and sequential blood samples from approximately 120 - 140 patients with CUP [ Time Frame: 18 months ]
  2. 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 ]
  3. 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 ]
  4. To perform whole genome sequencing in patients where enough tumour tissue is available to explore novel predictive and resistance biomarkers [ Time Frame: 18 months ]
  5. 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 ]
  6. Collect evidence investigating the most effective way to stratify patients with CUP onto treatment. [ Time Frame: 18 months ]
  7. To understand whether liquid biomarkers in CUP can be used to stratify patients and give prognostic information [ Time Frame: 18 months ]
  8. Develop a data collection repository within the NHS for patients with CUP [ Time Frame: 18 months ]

Biospecimen Retention:   Samples With DNA
Blood and tissue samples will be collected for translational research


Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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.
Criteria

Inclusion Criteria:

  • 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;

    1. The local pathology reports confirming compatibility with CUP diagnosis and the associated slides used for the diagnosis
    2. Discussion at a local CUP MDT confirming diagnosis
  • 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

Exclusion Criteria:

  • 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

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): NCT04750109


Contacts
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Contact: Natalie Cook 0161 918 7672 the-christie.cup-comp@nhs.net

Locations
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United Kingdom
Royal United Hospitals Bath NHS Foundation Trust Not yet recruiting
Bath, United Kingdom, BA1 3NG
Contact: Tania Tillett    07970 796440    the-christie.cup-comp@nhs.net   
Velindre Cancer Centre Not yet recruiting
Cardiff, United Kingdom, CF14 2TL
Contact: Robert Hughes    029 2061 5888    the-christie.cup-comp@nhs.net   
Edinburgh Cancer Centre Not yet recruiting
Edinburgh, United Kingdom, EH4 2XR
Contact: Sally Clive    0131 537 2263    the-christie.cup-comp@nhs.net   
UCL Cancer Institute Not yet recruiting
London, United Kingdom, WC1E 6BT
Contact: Kai-Keen Shiu    020 3456 7890    the-christie.cup-comp@nhs.net   
The Christie NHS Foundation Trust Recruiting
Manchester, United Kingdom, M20 4BX
Contact: Natalie Cook    0161 918 7672    the-christie.cup-comp@nhs.net   
Northern Centre for Cancer care Not yet recruiting
Newcastle, United Kingdom, NE7 7DN
Contact: Chris Jones    0191 2139257    the-christie.cup-comp@nhs.net   
Torbay Hospital Not yet recruiting
Torquay, United Kingdom, TQ2 7AA
Contact: Louise Medley    01803 655643    the-christie.cup-comp@nhs.net   
Sponsors and Collaborators
The Christie NHS Foundation Trust
Hoffmann-La Roche
ConcR
Durham University
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Responsible Party: The Christie NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT04750109    
Other Study ID Numbers: CFTSp188
First Posted: February 11, 2021    Key Record Dates
Last Update Posted: August 6, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms, Unknown Primary
Neoplasms
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes