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

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

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Prostatic Neoplasms
• Intervention / Treatment: Drug: Degarelix (LHRH antagonist); Device: EndoPAT2000; Drug: LHRH agonist

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel, 31096
    • Rambam Health Care Campus
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center - Beilinson Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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:

  1. Myocardial infarction
  2. Ischaemic or Haemorrhagic cerebrovascular conditions
  3. Arterial embolic and thrombotic events,
  4. Ischaemic heart disease
  5. Prior coronary artery or iliofemoral artery revascularization (percutaneous or surgical procedures)
  6. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in testosterone level		Baseline, and after three, six and twelve months of treatment initiation
Change in gonadotropins levels	LH	Baseline, and after three, six and twelve months of treatment initiation
Change in PSA value	Prostate-specific antigen	Baseline, and after three, six and twelve months of treatment initiation
Change in BMI	Body Mass Index	Baseline, and after three, six and twelve months of treatment initiation
Change in Quality Of Life score	As assessed by the FACT-P quality of life questionnaire	Baseline, and after three, six and twelve months of treatment initiation

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Collaborators: Ferring Pharmaceuticals

Publications and helpful links

General Publications

• Zengerling F, Jakob JJ, Schmidt S, Meerpohl JJ, Blumle A, Schmucker C, Mayer B, Kunath F. Degarelix for treating advanced hormone-sensitive prostate cancer. Cochrane Database Syst Rev. 2021 Aug 5;8(8):CD012548. doi: 10.1002/14651858.CD012548.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: June 8, 2015
• First Submitted That Met QC Criteria: June 15, 2015
• First Posted (Estimate): June 18, 2015

Study Record Updates

• Last Update Posted (Actual): June 12, 2019
• Last Update Submitted That Met QC Criteria: June 11, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Prostate Cancer; Degarelix
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Cardiovascular Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones; Prolactin Release-Inhibiting Factors
• Other Study ID Numbers: 0102-15-RMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED