Endothelial Function in Prostate Cancer Patients on Degarelix vs. Luteinizing Hormone-Releasing Hormone Agonists

Study Overview
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Brief Summary
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The purpose of this study is to test whether Degarelix is associated with less endothelial dysfunction (an intermediate in the development of cardiac disease) and cardiovascular biomarkers compared to LHRH agonists.

Detailed Description
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This is a national multicenter randomized open-label superiority study of the use of Degarelix compared to LHRH agonists among men with advanced prostate cancer and pre-existing cardiovascular disease. Patients will be stratified based on baseline endothelial function and presence prostate cancer metastasis. Study population: Subjects with pre-existing cardiovascular disease with locally advanced or metastatic prostate cancer and scheduled to start Androgen Deprivation Therapy (ADT). Patients already on ADT will be excluded. subjects will receive either two initial loading doses of 120mg Degarelix for 1 month followed by 80mg monthly for eleven additional months or an LHRH agonist at the discretion of the treating Urologist/Oncologist for 1 year. Follow-up visits will occur every 3 months. A blood sample for Prostate-specific antigen (PSA), cardiac biomarkers and rectal examination will be performed each visit. At baseline 6 and 12 months EndoPAT2000 measurements will be taken.

Official Title
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A Pilot Study on Endothelial Function and Cardiovascular Biomarkers in Prostate Cancer (PCa) Patients, With Pre-existing Cardiovascular Disease, Treated With Degarelix vs. Luteinizing Hormone-Releasing Hormone (LHRH) Agonists

Conditions
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Prostatic Neoplasms, Cardiovascular Diseases

Intervention / Treatment
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* Drug: Degarelix (LHRH antagonist)
* Drug: LHRH agonist
* Device: EndoPAT2000


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male patients with locally advanced or metastatic prostate cancer or high-risk prostate cancer. Scheduled to start ADT for a period of at least one year. Subject has a history of one or more of the following: Myocardial infarction Ischaemic or Haemorrhagic cerebrovascular conditions Arterial embolic and thrombotic events, Ischaemic heart disease Prior coronary artery or iliofemoral artery revascularization (percutaneous or surgical procedures) Peripheral vascular disease (e.g. significant stenosis (ABPI<0.9), claudication, prior vascular surgery/intervention) Life expectancy of over 12 months. WHO performance status of 0-2 Subject is able and has agreed to sign a consent form. Exclusion Criteria: Prior use of ADT. However, prior use of anti-androgens such as Casodex, Chimax, Drogenil, and Cyprostat will be allowed. Prior use of dutasteride/finasteride in past 6 months Known allergic reaction to Degarelix. Any psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow-up schedule.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Degarelix (LHRH antagonist)<br>Degarelix (LHRH antagonist) EndoPAT2000 | Drug: Degarelix (LHRH antagonist)<br>* Two initial loading doses of 120mg Degarelix for 1 month followed by 80mg monthly for eleven additional months.<br>* Other names: Firmagon;Device: EndoPAT2000<br>* Peripheral arterial plethysmography using an EndoPAT2000 device<br>* Other names: Peripheral arterial plethysmography;|
| Active Comparator: LHRH agonist<br>LHRH agonist at the discretion of the treating Urologist/Oncologist EndoPAT2000 | Drug: LHRH agonist<br>* LHRH agonist at the discretion of the treating Urologist/Oncologist for 1 year.<br>* Other names: Luteinizing hormone-releasing hormone agonist;Device: EndoPAT2000<br>* Peripheral arterial plethysmography using an EndoPAT2000 device<br>* Other names: Peripheral arterial plethysmography;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Reactive Hyperemia Index from baseline to twelve months | the Reactive Hyperemia Index is a measure of endothelial function. It will be measured using the EndoPAT2000 | Baseline, and twelve months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in High sensitivity troponin (hsTn) value | High sensitivity troponin (hsTn) is a biomarker for acute myocardial injury | Baseline, and after three, six and twelve months of treatment initiation | 
| Change in C-reactive protein value | C-reactive protein is a biomarker for inflammation | Baseline, and after three, six and twelve months of treatment initiation | 
| Change in D-dimer value | D-dimer is a biomarker for coagulation system activation | Baseline, and after three, six and twelve months of treatment initiation | 
| Change in N-terminal pro-brain natriuretic peptide (NT-proBNP) value | N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker for myocardial strain | Baseline, and after three, six and twelve months of treatment initiation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, Cardiovascular disease, Degarelix