Circulating Tumour Cells as Biomarkers to Predict Prostate Cancer Metastasis for Treatment Stratification of Cancer (C-ProMeta-1)

Circulating Tumour Cells as Biomarkers to Predict Prostate Cancer Metastasis for Treatment Stratification of Localised Cancer

The goal of this study is to establish the value of Circulating Tumour Cell (CTC) positivity in predicting post-RP treatment failure, including BCR and new lesions detected by cancer imaging. We plan to recruit participants who will undergo Radical Prostatectomy (RP). Participants will have their blood samples taken just before surgery and 3 months after the surgery to test for CTCs. Then participants will be followed-up for cancer progression information at 3 month intervals for the first year then yearly intervals after that. Their PSA will be observed over time.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Diagnostic test: CTC Blood Test

Detailed Description

This is a single site, double-blinded, prospective, paired cohort study. Participating patients and clinicians involved in treatment or management will be blinded to the CTC results, to avoid influencing standard patient treatment, management, and progression outcomes after RP.

Patients will be recruited (months 1-24) at UCLH, where the UK largest urological surgery centre is located and performs robot-assisted RP on PCa patients referred from several regional hospitals. The clinical team at UCLH will identify eligible patients who will be approached by the clinical research fellow (CRF) employed on the research project or the clinical care team for informed consent using the consent forms specifically designed for this project for blood collection and future research. Non-metastatic disease will be based on the current standard diagnostic imaging methods including CT/MRI and PSMA-PET/bone scan. A pre-surgery PSA test will be performed routinely at UCLH.

2 x 10 ml blood samples will be collected (months 1-27) using the lavender cap EDTA tube according to our established method from each consented patient by the CRF or the clinical care team at UCLH during the pre- and post-RP PSA test blood sampling, and taken to the laboratory at Barts Cancer Institute, John Vane Science Centre, Charterhouse Square either by the CRF, a tissue bank acquisition officer (TBAO)(in the absence of the CRF) or the postdoc (anonymise samples transfer in the absence of CRF and TBAO) under the signed material transfer agreement (MTA), at room temperature. The samples will be transported in designated sample carrier using a taxi service. No public transport is to be used for moving samples between sites.

• Study Type: Observational
• Enrollment (Estimated): 490

Contacts and Locations

• Study Contact: Name: Thomas Duffy, MSc; Phone Number: +44 7512745637; Email: t.duffy@qmul.ac.uk
• Study Contact Backup: Name: Yong-Jie Lu; Phone Number: +44 20 7882 3597; Email: y.j.lu@qmul.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • University College London Hospitals
    • Contact: Greg Shaw; Email: gregshaw@nhs.net
    • Contact: Tarek Al Hammouri; Email: tarek.al-hammouri@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

In order to recruit patients meeting the eligibility criteria, it will be necessary to screen all patients in the participating centre who are diagnosed with high risk localised PCa based on the current European Urology Association classification system and who have been scheduled for surgery to completely remove the cancer in the prostate gland.

Description

Inclusion Criteria:

• High/High intermediate risk non-metastatic risk localised PCa based on the EAU stratification system
• Scheduled for robot-assisted RP
• Informed consent

Exclusion Criteria:

• With other co-occurring cancers
• Neo-adjuvant ADT
• Adjuvant ADT

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
RP Treatment cohort; We will use participants who have been deemed eligible for radical prostatectomy based on the current European Urology Association classification system, and who have been scheduled for surgery to completely remove the cancer in the prostate gland.	Diagnostic test: CTC Blood Test; We will draw blood to measure the level of Circulating Tumour Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-RP treatment failure during the first 4.5 years of follow up from start of recruitment.	Post-RP treatment failure is defined as a PSA ≥ 0.2mg/ml at the routine PSA test 3 months after RP (commonly called 'failure to nadir') and remaining at this level or further increase afterwards without further treatment, or imaging detected appearance of cancer lesions. Cancer lesions detected by imaging without a PSA rise might include neuroendocrine PCa and lesions detected by PSAM-PET. This combined post-RP treatment failure primary endpoint will maximally capture all the clinically significant cancer appearance events.	4.5 years from the start of recruitment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BCR during the first 4.5 years of follow up	BCR during the first 4.5 years of follow up: PSA ≥ 0.2ng/ml at any time post-RP and remaining at this level or further increase afterwards without further treatment.	4.5 years
Metastasis free survival (4.5yrs)	Metastasis (any location)-free survival during the first 4.5 years of follow up. Only 5% of subjects with distant metastasis event (based on traditional imaging technologies) within this time frame (4-6).	4.5 years
Metastasis free survival (10yrs)	Metastasis (any location)-free survival at 10 years follow up. to confirm that metastatic event rates have increased among the positives, i.e. a declining rate of "false positives".	10 years
Deaths (4.5yrs)	Deaths from any cause during the first 4.5 years of follow up	4.5 years
10 year survival	Overall survival at 10 years of follow up.	10 years
Prostate cancer deaths (4.5yrs)	Prostate cancer specific deaths during the first 4.5 years of follow up. Expected to be 2% or less based on previous studies in the post RP context.	4.5 years

Collaborators and Investigators

• Sponsor: Queen Mary University of London
• Collaborators: University College London Hospitals
• Investigators: Principal Investigator: Greg Shaw, University College London Hospitals

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: September 5, 2022
• First Submitted That Met QC Criteria: September 5, 2022
• First Posted (Actual): September 9, 2022

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Neoplastic Processes; Neoplasm Metastasis; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Neoplastic Cells, Circulating
• Other Study ID Numbers: 19/LO/0994; 140998 (Other Identifier: IRAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share the IPD after publication
• IPD Sharing Time Frame: As soon as possible after publishing the main study
• IPD Sharing Access Criteria: Reviewed by study management group for clinical/scientific benefit.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No