Cardiovascular Events in GnRH Agonist vs. Antagonist

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

Sponsors

Lead Sponsor: Rabin Medical Center

Collaborator: Ferring Pharmaceuticals

Source 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?

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.

Overall Status Not yet recruiting
Start Date January 17, 2020
Completion Date January 17, 2023
Primary Completion Date January 17, 2023
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
time to first cardiovascular event 1 year
Secondary Outcome
Measure Time Frame
time to first MACCE event 1 year
cardiac echocardiography 1 year
Hormonal Profile 1 year
NTproBNP levels 1 year
Adverse events 1 year
PSA levles 1 year
BMI 1 year
Quality of life: FACT-P questionnaire 1 year
Glucose profile 1 year
Cholesterol levles 1 year
Enrollment 80
Condition
Intervention

Intervention Type: Drug

Intervention Name: Degarelix

Description: Treatment will start with two injections of 120 mg each followed by maintenance of a single injection of 80 mg administered every 28 days

Arm Group Label: Degarelix

Other Name: Firmagon

Intervention Type: Drug

Intervention Name: GnRH agonist

Description: GnRH agonist at the discretion of the treating Urologist/Oncologist for 1 year

Arm Group Label: GnRH-agonist

Eligibility

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.

Gender: Male

Minimum Age: 18 Years

Maximum Age: 90 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
David Margel, MD, PhD Principal Investigator Rabin Medical Center
Overall Contact

Last Name: Yaara Ber, PhD

Phone: 972-39376551

Email: [email protected]

Location
Facility: Contact: Contact Backup: Investigator: Rabin Medical Center - Beilinson Hospital Yaara Ber, PhD 972-3-9376553 [email protected] David Margel, MD, PhD Principal Investigator Eli Rosenbaum, MD Sub-Investigator Victoria Neiman, MD Sub-Investigator Shay Golan, MD Sub-Investigator Daniel Kedar, MD Sub-Investigator Jack Baniel, MD Sub-Investigator
Location Countries

Israel

Verification Date

October 2019

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Degarelix

Type: Experimental

Description: GnRH Antagonist

Label: GnRH-agonist

Type: Active Comparator

Description: GnRH Agonist

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Single (Outcomes Assessor)

Source: ClinicalTrials.gov