Enabling Genomic Testing in Cancer of Unknown Primary (EGGCUP)

Cancer of Unknown Primary (CUP) is where cancer cells are found in the body but the place the cancer began is not known. It is the 6th leading cause of cancer death in the UK and the prognosis is poor with a median survival of 6-9 months. There is a higher than average incidence of CUP in the North West (NW) of England (population of 7.4 million). Precision medicine has transformed treatment strategies in known tumour types, however in CUP there remains an urgent need to better understand CUP molecular characteristics to establish potential roles for novel therapeutic strategies. Treatment options remain limited due to difficulties in determining the primary site of the tumour and the lack of access to validated biomarkers. Access to good-quality tissue for molecular profiling remains a huge challenge in CUP. The emergence of liquid biopsies (sequence DNA in a blood test) as a source of biomarkers is also gaining rapid ground and this study aims to explore the potential utility of liquid biopsies in CUP.

Study Overview

• Status: Recruiting
• Conditions: Cancer of Unknown Primary; Neoplasm, Unknown Primary
• Intervention / Treatment: Diagnostic test: Gene panel array; Other: Blood Sample Collection

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: EGG CUP Study Team; Phone Number: +44 161 918 7672; Email: the-christie.egg-cup@nhs.net

Study Locations

• United Kingdom
  • Blackpool, United Kingdom
    • Recruiting
    • Blackpool Teaching Hospitals NHS Foundation Trust
    • Principal Investigator: Pavel Bezecny
  • Manchester, United Kingdom
    • Recruiting
    • Northern Care Alliance NHS Foundation Trust
    • Principal Investigator: Paul O'Donnell
  • Morecambe, United Kingdom
    • Recruiting
    • University Hospitals of Morecambe Bay NHS Trust
    • Principal Investigator: N Chan Ton
  • Preston, United Kingdom
    • Recruiting
    • Lancashire Teaching Hospitals NHS Foundation Trust
    • Principal Investigator: Catherine Mitchell
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4BX
      • Recruiting
      • The Christie NHS Foundation Trust
      • Principal Investigator: Natalie Cook
  • Merseyside
    • Liverpool, Merseyside, United Kingdom
      • Recruiting
      • The Clatterbridge Cancer Centre NHS Foundation Trust
      • Principal Investigator: Eliyaz Ahmed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with cancer of unknown primary

Description

Inclusion Criteria:

1. Aged 16 years or over
2. Written informed consent according to ICH/GCP and national regulations
3. ECOG Performance status 0-2

4. Confirmed diagnosis of CUP as per the ESMO guidelines. 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
5. Availability of archival tumour histological report
6. Willingness to provide blood samples on up to two occasions during the study

Exclusion Criteria:

1. Patient with an immunohistochemistry profile that provides a definitive clinical indication of a primary cancer with a specific treatment
2. Known HIV, Hepatitis B, C positive, due to the difficulties in handling high-risk specimens
3. Patients who are unable to provide fully informed written consent
4. 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
5. Bleeding diathesis (patients' on anticoagulation are permitted to enter the trial if anticoagulation can be safely managed to enable blood sampling)
6. Conditions in which blood sampling may increase risk of complications for the patients and/or investigator

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
All participants; Blood sample collection for gene panel array testing and simultaneous research purposes	Diagnostic test: Gene panel array; Blood sample collection for gene panel testing; Other: Blood Sample Collection; Blood sample collection for research purposes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the utility of cfDNA molecular profiling in patients diagnosed with CUP	Percentage of patients with adequate cfDNA yields measured using FoundationOne®️ Liquid CDx testing of blood samples obtained at baseline or progression timepoints; Percentage of patients with actionable genomic alterations measured using FoundationOne®️ Liquid CDx testing of blood samples obtained at baseline or progression timepoints; Percentage of patients eligible for personalised treatment options or enrolment on a UK-based clinical trial because of the cfDNA results, measured using FoundationOne®️ Liquid CDx testing of blood samples obtained at baseline or progression timepoints	33 months of recruitment + 12 months follow up period or 1 December 2027 whichever comes first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Data collection repository of readily available information on trails/treatments for patients diagnosed with CUP	Develop a data collection repository and readily available information on trials/treatments for patients diagnosed with CUP to be shared at monthly trial management group meetings to ensure that investigators are aware of suitable trial opportunities	33 months of recruitment + 12 months follow up period or 1 December 2027 whichever comes first
Incorporate molecular genomics into routine practice	Routinely incorporate molecular genomics as standard of care in patients diagnosed with CUP following FoundationOne®️ CDx or FoundationOne®️ Liquid CDx at baseline and FoundationOne®️ Liquid CDx at progression	33 months of recruitment + 12 months follow up period or 1 December 2027 whichever comes first
Document and feedback genomic results to treating team and patients	Documentation and feedback of genomic results/GTAB outcomes to all patients and treating teams following FoundationOne®️ CDx or FoundationOne®️ Liquid CDx at baseline, and FoundationOne®️ Liquid CDx at progression	33 months of recruitment + 12 months follow up period or 1 December 2027 whichever comes first

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of novel biomarkers to help in the diagnosis and treatment of patients diagnosed with CUP	Collect samples to be used to investigate novel biomarkers to help in the diagnosis and treatment in patients diagnosed with CUP	Future research sample collection performed at baseline visit. 33 months of recruitment or 1st December 2026 whichever comes first

Collaborators and Investigators

• Sponsor: The Christie NHS Foundation Trust
• Collaborators: Hoffmann-La Roche; University of Manchester; National Institute for Health Research, United Kingdom
• Investigators: Principal Investigator: Natalie Cook, The University of Manchester

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: August 27, 2024
• First Submitted That Met QC Criteria: November 18, 2024
• First Posted (Actual): November 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cancer; Cancer of unknown primary
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplastic Processes; Neoplasm Metastasis; Pathological Conditions, Signs and Symptoms; Neoplasms; Neoplasms, Unknown Primary
• Other Study ID Numbers: CFTSp213; ISRCTN42910771 (Registry Identifier: International Standard Randomised Controlled Trial Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No