Enabling Genomic Testing in Cancer of Unknown Primary

Recruiting

• Conditions: Cancer of Unknown Primary; Neoplasm, Unknown Primary

• Registration Number: NCT06695494
• Lead Sponsor: The Christie NHS Foundation Trust

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-08-15
• Study First Submitted: 2024-08-27
• Study First Submitted QC: 2024-11-18
• Study First Posted: 2024-11-19
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-08
• Last Update Posted: 2025-01-09
• Primary Completion: 2026-12-01
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Evaluate the utility of cfDNA molecular profiling in patients diagnosed with CUP	33 months of recruitment + 12 months follow up period or 1 December 2027 whichever comes first	1. Percentage of patients with adequate cfDNA yields measured using FoundationOne®️ Liquid CDx testing of blood samples obtained at baseline or progression timepoints; 2. Percentage of patients with actionable genomic alterations measured using FoundationOne®️ Liquid CDx testing of blood samples obtained at baseline or progression timepoints; 3. 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

Secondary Outcome Measures

Name	Time	Method
Data collection repository of readily available information on trails/treatments for patients diagnosed with CUP	33 months of recruitment + 12 months follow up period or 1 December 2027 whichever comes first	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
Incorporate molecular genomics into routine practice	33 months of recruitment + 12 months follow up period or 1 December 2027 whichever comes first	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
Document and feedback genomic results to treating team and patients	33 months of recruitment + 12 months follow up period or 1 December 2027 whichever comes first	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

Trial Locations

Locations (6)

The Christie NHS Foundation Trust; 🇬🇧 Manchester, Greater Manchester, United Kingdom

The Clatterbridge Cancer Centre NHS Foundation Trust; 🇬🇧 Liverpool, Merseyside, United Kingdom

Blackpool Teaching Hospitals NHS Foundation Trust; 🇬🇧 Blackpool, United Kingdom

Northern Care Alliance NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

University Hospitals of Morecambe Bay NHS Trust; 🇬🇧 Morecambe, United Kingdom

Lancashire Teaching Hospitals NHS Foundation Trust; 🇬🇧 Preston, United Kingdom