Clinical trial NCT04182594: Cardiovascular Events in GnRH Agonist vs. Antagonist
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hormone Sensitive Prostate Cancer
Prostate Cancer
Cardiac Event
Lead sponsor: Rabin Medical Center
Sponsor class: OTHER
Collaborators: name: Ferring Pharmaceuticals
First posted: 2019-12-02
Enrollment: 80
Sex: MALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: time to first cardiovascular event
timeFrame: 1 year
Secondary outcomes:
measure: time to first MACCE event
timeFrame: 1 year
measure: cardiac echocardiography
timeFrame: 1 year
measure: Hormonal Profile
timeFrame: 1 year
measure: NTproBNP levels
timeFrame: 1 year
measure: Adverse events
timeFrame: 1 year
measure: PSA levles
timeFrame: 1 year
measure: BMI
timeFrame: 1 year
measure: Quality of life: FACT-P questionnaire
timeFrame: 1 year
measure: Glucose profile
timeFrame: 1 year
measure: Cholesterol levles
timeFrame: 1 year
Other outcomes:
Locations:
city: Petah Tikva
country: Israel
facility: Rabin Medical Center - Beilinson Hospital
Study officials:
affiliation: Rabin Medical Center
name: David Margel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.