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Cardiovascular Events in GnRH Agonist vs. Antagonist

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ClinicalTrials.gov Identifier: NCT04182594
Recruitment Status : Not yet recruiting
First Posted : December 2, 2019
Last Update Posted : December 2, 2019
Sponsor:
Collaborator:
Ferring Pharmaceuticals
Information provided by (Responsible Party):
Rabin Medical Center

Brief Summary:
The purpose of this study is to test if the use of Degarelix for 1 year associated with a lower rate of cardiovascular toxicity compared to Gonadotropin-releasing hormone (GnRH) agonists in patients with advanced prostate cancer and cardiovascular risk factors, receiving combination therapy of Androgen deprivation therapy (ADT) and second line hormonal or chemotherapy?

Condition or disease Intervention/treatment Phase
Hormone Sensitive Prostate Cancer Prostate Cancer Cardiac Event Drug: Degarelix Drug: GnRH agonist Phase 2

Detailed Description:

Study design: Randomized phase-2, open label superiority study of the use of ADT combined with second line hormonal or chemotherapy in men with advanced prostate cancer and pre-existing cardiovascular risks.

Study population: Subjects with pre-existing cardiovascular risk with locally advanced or metastatic prostate cancer and scheduled to start ADT in combination with either second line hormonal or chemotherapy. We will exclude patients with use of ADT 6 months prior to randomization.

Intervention- Two initial loading doses of 120mg Degarelix for 1 month followed by 80mg monthly for eleven additional months.

Control- GnRH agonist at the discretion of the treating Urologist/Oncologist for 1 year.

Study Time line- The intervention phase will be for one year. During this year, follow-up visits will occur every 3 months. At each visit, we will assess the occurrence of cardiac-related events. In addition, Protein-specific Antigen (PSA) test will be performed each visit. At baseline, 3, 6 and 12 months cardiac biomarkers and lab measurements will be taken. Echocardiogram will be performed at baseline, 6, 9 and 12 months. In addition, cardio-vascular related events and hospitalizations will be monitored for additional 5 years.

Primary endpoint: To compare time to first cardiovascular event of patients with advanced prostate cancer treated for one year with Degarelix vs. GnRH agonist. This will be a composite outcome composed of: Death, Cerebrovascular accident (CVA), Myocardial infarction (MI), Transient ischemic attack (TIA), cardiac emergency room visits, heart catheterization.

Secondary endpoints: To compare time to first major adverse cardiovascular and cerebrovascular event (MACCE)- (Death, CVA, MI, heart catheterization with stent) as estimated by the cumulated probability at the 1-year timepoint of patients with advanced prostate cancer treated for one year with Degarelix vs. LHRH agonist. To compare cardiovascular biomarker levels of patients with advanced prostate cancer treated with Degarelix vs. GnRH agonist. To compare change in cardiac function as measured by Echocardiography in 6,9 and 12 months.

Study impact- This study has the potential to cause a paradigm shift. If we indeed demonstrate that Degarelix is associated with less cardiovascular toxicity with clinical significance, we expect that most urologist, as well as patients, will prefer Degarelix over all other ADT.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase-II, Randomized, Assessor-Blind, Controlled Trial Comparing the Occurrence of Cardiovascular Events in Patients With Prostate Cancer and Cardiovascular Risk Factors Receiving Degarelix or GnRH Agonist
Estimated Study Start Date : January 17, 2020
Estimated Primary Completion Date : January 17, 2023
Estimated Study Completion Date : January 17, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Degarelix

Arm Intervention/treatment
Experimental: Degarelix
GnRH Antagonist
Drug: Degarelix
Treatment will start with two injections of 120 mg each followed by maintenance of a single injection of 80 mg administered every 28 days
Other Name: Firmagon

Active Comparator: GnRH-agonist
GnRH Agonist
Drug: GnRH agonist
GnRH agonist at the discretion of the treating Urologist/Oncologist for 1 year




Primary Outcome Measures :
  1. time to first cardiovascular event [ Time Frame: 1 year ]
    To compare time to first cardiovascular event as estimated by the cumulated probability at the 1-year time-point of patients with advanced prostate cancer treated for one year with Degarelix vs. GnRH agonist. This will be a composite outcome composed of: Death, CVA, MI, TIA, cardiac emergency room visits, heart catheterization.


Secondary Outcome Measures :
  1. time to first MACCE event [ Time Frame: 1 year ]

    To compare time to first MACCE event as estimated by the cumulated probability at the 1-year timepoint of patients with advanced prostate cancer treated with Degarelix vs. GnRH agonist and combination therapy.

    MACCE will be defined as:

    1. Death of any cause
    2. MI
    3. CVA
    4. Percutaneous coronary intervention, (PCI) with stent insertion

  2. cardiac echocardiography [ Time Frame: 1 year ]
    To compare change in ejection fraction (EF) as measured by cardiac echocardiography of patients with advanced prostate cancer treated with Degarelix vs. GnRH agonist, at baseline, six-, nine- and twelve-months of combination treatment.

  3. Hormonal Profile [ Time Frame: 1 year ]
    To compare testosterone serum levels (ng/dL) of patients with advanced prostate cancer treated with Degarelix vs. GnRH agonist, at baseline, three-, six- and twelve-months of combination treatment.

  4. NTproBNP levels [ Time Frame: 1 year ]
    To compare levels of NTproBNP (pg/mL) in patients with advanced prostate cancer treated with Degarelix vs. GnRH agonist, at baseline, three-, six-, nine- and twelve-months of combination treatment.

  5. Adverse events [ Time Frame: 1 year ]
    To compare rate of other adverse events in patients with advanced prostate cancer treated with Degarelix vs GnRH agonist and combination therapy.

  6. PSA levles [ Time Frame: 1 year ]
    To compare PSA serum levels (ng/mL) of patients with advanced prostate cancer treated with Degarelix vs. GnRH agonist, at baseline, three-, six- nine- and twelve-months of combination treatment.

  7. BMI [ Time Frame: 1 year ]
    To compare changes in body mass index (BMI) in patients with advanced prostate cancer treated with Degarelix vs. GnRH agonist, at baseline, three-, six- and twelve-months of combination treatment.

  8. Quality of life: FACT-P questionnaire [ Time Frame: 1 year ]
    To compare the quality of life by self-reported FACT-P questionnaire, by patients with advanced prostate cancer treated with Degarelix vs. GnRH agonist, at baseline, three-, six- and twelve-months of combination treatment

  9. Glucose profile [ Time Frame: 1 year ]
    To compare glucose levels (mg/dL) in patients with advanced prostate cancer treated with Degarelix vs GnRH agonist, at baseline, three-, six- and twelve-months of combination treatment.

  10. Cholesterol levles [ Time Frame: 1 year ]
    To compare Cholesterol serum levels (mg/dL) of patients with advanced prostate cancer treated with Degarelix vs. GnRH agonist, at baseline, three-, six- nine- and twelve-months of combination treatment.



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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Locally advanced high-risk prostate cancer OR metastatic prostate cancer patients.
  2. Patients are scheduled to receive a combination of either

    1. primary ADT for 12 months + either chemotherapy with docetaxel OR
    2. primary ADT for 12 months + second line hormonal treatment with abiraterone/ enzalutamide/ apalutamide
  3. Patients with a medical history of either 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(
    7. Two out of three cardiovascular risk factors: hypertension, diabetes, current smoking.
  4. Patients age 18-90 years.
  5. Life expectancy of over 12 months.
  6. WHO performance status of 0-2
  7. Subject is able and has agreed to sign a consent form.

Exclusion Criteria:

  1. Prior use of ADT in past 6 months prior to randomization. We will, however, allow prior use of anti-androgens such as Casodex, Chimax, Drogenil, and Cyprostat.
  2. Known allergic reaction to Degarelix.
  3. Any psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow-up schedule.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04182594


Contacts
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Contact: Yaara Ber, PhD 972-39376551 yaaraba1@clalit.org.il

Locations
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Israel
Rabin Medical Center - Beilinson Hospital
Petah Tikva, Israel, 4941492
Contact: Yaara Ber, PhD    972-3-9376553    yaaraba1@clalit.org.il   
Contact: David Margel, MD, PhD    972-3-9376553    sdmargel@gmail.com   
Principal Investigator: David Margel, MD, PhD         
Sub-Investigator: Eli Rosenbaum, MD         
Sub-Investigator: Victoria Neiman, MD         
Sub-Investigator: Shay Golan, MD         
Sub-Investigator: Daniel Kedar, MD         
Sub-Investigator: Jack Baniel, MD         
Sponsors and Collaborators
Rabin Medical Center
Ferring Pharmaceuticals
Investigators
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Principal Investigator: David Margel, MD, PhD Rabin Medical Center
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Rabin Medical Center
ClinicalTrials.gov Identifier: NCT04182594    
Other Study ID Numbers: 0670-19-RMC
First Posted: December 2, 2019    Key Record Dates
Last Update Posted: December 2, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases