ExPeCT: Exercise, Prostate Cancer and Circulating Tumour Cells
Study Details
Study Description
Brief Summary
Obesity, known to be associated with a pro-inflammatory, pro-thrombotic humoral milieu, confers a worse prognosis in prostate cancer (PrCa). Circulating tumour cells (CTCs) are identified in the blood in advanced cancer. Their quantitation provides prognostic information. "Cloaking" of CTCs by adherent platelets impedes natural killer (NK)-cell clearance of CTCs from the circulation, enhancing metastatic spread. NK-cell function in blood and in solid organs is quantitatively and qualitatively reduced in obesity. Platelet cloaking may be enhanced in obesity due to the pro-inflammatory, pro-thrombotic state, and may be a mechanism for worse cancer-specific outcomes in this group. Obesity and its biochemical effects may be influenced by lifestyle changes such as exercise. Physical activity reduces levels of systemic inflammatory mediators and so an aerobic exercise intervention may represent an accessible and cost-effective means of ameliorating the pro-inflammatory effects of obesity. The ExPeCT trial will determine if a prescribed exercise intervention can ameliorate the degree of platelet cloaking in obese and non-obese men with advanced prostate cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
The overarching hypothesis is that enhanced platelet cloaking of circulating tumour cells in obese men with prostate cancer, due to increased systemic inflammation, is a mechanism underlying worse prognosis of cancer in these patients.
The investigators aim to test the following four hypotheses, dividing the experimental and analytical work into four separate projects.
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Platelet cloaking of circulating PrCa tumour cells is more prominent in men with obesity than without
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Regular exercise can ameliorate platelet cloaking
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The degree of platelet cloaking varies with levels of systemic and primary tumour inflammation and coagulability
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Expression of an obesity-associated lethality gene signature leads to variation in platelet cloaking
For the first hypothesis, 200 men with metastatic PrCa will be recruited, and divided into exposed and non-exposed groups based on body mass index (BMI >25). The objective will be to enumerate CTCs and quantify the degree of platelet cloaking in exposed and non-exposed groups, and to draw meaningful comparisons between the two.
For the second hypothesis, the objective will be to determine to what extent the number of CTCs and the degree of platelet cloaking varies in exposed and non-exposed groups following a supervised exercise intervention, and to compare this with a non-exercised comparison group. The exercise intervention will prescribe moderate intensity aerobic exercise that will be supervised once per week for 3 months and completed independently at home for a further 3 months. Patients will wear Polar heart rate monitors to monitor exercise prescription and progression. Assessments including blood sampling and quality of life questionnaires will be completed at baseline, 3 months and 6 months.
For the third hypothesis, the objective will be to build a serological, haematological and immunological picture of the state of systemic inflammation and coagulability, and the degree of inflammation within the prostate gland. Furthermore, the investigators intend to correlate and compare these variables with the results of the first and second objectives, in order to determine whether the number of CTCs and the degree of platelet cloaking varies with changes in the inflammatory / coagulatory milieu.
For the fourth hypothesis, the objective will be to determine whether the expression profile of a number of lethality-associated genes, known to be associated with PrCa progression, coagulation and stem-cell like phenotype, correlates with the number of CTCs and the degree of their cloaking by platelets.
CTC numbers and the degree of platelet cloaking will be common denominators which anchor these four objectives together and enable comparison between them.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Exercise group 6 month supervised and home based moderate intensity aerobic exercise programme |
Behavioral: Exercise
6 month supervised and home based aerobic exercise intervention
|
| No Intervention: Control Non-exercising control group receiving usual care |
Outcome Measures
Primary Outcome Measures
- Change in Platelet cloaking of Circulating Tumour Cells [Change from baseline in platelet cloaking of circulating tumours cells at 3 months and 6 months]
Enumeration of circulating tumour cells and degree of platelet cloaking of CTCs
Secondary Outcome Measures
- Change in systemic inflammation [Change in cytokines from baseline in inflammation at 3 months and 6 months]
Blood samples will be taken from participants at each assessment and analysed by multi-plex assays for levels of cytokines (TNF-alpha and interleukin (IL)-6
- Change in Quality of Life Questionnaire [Change from baseline in quality of life at 3 months and 6 months]
Participants will complete quality of life questionnaires assessing a range of issues including sleep, diet quality and physical activity at each assessment
Eligibility Criteria
Criteria
Inclusion Criteria:
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Written informed consent obtained before any study-related procedures
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Age ≥ 18 years and male
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Histologically confirmed diagnosis of prostate adenocarcinoma
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Metastatic disease as confirmed by CT/MRI or by bone scan
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Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 28 days prior to randomisation
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Capable of participating safely in the proposed exercise intervention as assessed and signed off by a treating physician involved in ExPeCT recruitment.
Exclusion Criteria:
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No history of radical prostatectomy
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No previous diagnosis of any other malignant tumour (patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded provided they have undergone complete resection)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Adelaide and Meath Incorporating the National Children's Hospital | Tallaght | Dublin | Ireland | 24 |
| 2 | St James's Hospital | Dublin | Ireland | 8 | |
| 3 | Beaumont Hospital | Dublin | Ireland | ||
| 4 | Mater Misericordiae University Hospital | Dublin | Ireland | ||
| 5 | St Luke's Hospital | Dublin | Ireland | ||
| 6 | Guy's St Thomas | London | United Kingdom |
Sponsors and Collaborators
- University of Dublin, Trinity College
Investigators
- Principal Investigator: Stephen Finn, University of Dublin, Trinity College
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 202370