Clinical trial NCT02663908: A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease
Official title: A Multi-Center, Randomized, Assessor-Blind, Controlled Trial Comparing the Occurrence of Major Adverse Cardiovascular Events (MACEs) in Patients With Prostate Cancer and Cardiovascular Disease Receiving Degarelix (Gonadotropin-Releasing Hormone (GnRH) Receptor Antagonist) or Leuprolide (GnRH Receptor Agonist)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Prostate Cancer
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Memorial Sloan Kettering Cancer Center
name: Duke Clinical Research Institute
First posted: 2016-01-26
Enrollment: 545
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to test if a marketed drug for advanced prostate cancer (FIRMAGON) can reduce the risk of cardiovascular complications as compared to another marketed drug for advanced prostate cancer (LUPRON DEPOT) in subjects with prostate cancer and cardiovascular disease.


Eligibility criteria: Inclusion Criteria:

* Advanced prostate cancer
* Indication to initiate androgen deprivation therapy (ADT)
* Predefined cardiovascular disease

Exclusion Criteria:

* Previous or current hormonal management of prostate cancer (unless terminated at least 12 months prior to trial)
* Acute cardiovascular disease in the previous 30 days

Primary outcomes:
measure: Time From Randomization to the First Confirmed (Adjudicated) Occurrence of the Composite Major Adverse Cardiovascular Event (MACE) Endpoint; Percentage of Observed Subjects With Outcome Measure Events During the Trial
timeFrame: Randomization to Day 336 (end-of-trial)
Secondary outcomes:
measure: Time From Randomization to the First Confirmed (Adjudicated) Occurrence of Cardiovascular (CV)-Related Death, Non-fatal Myocardial Infarction or Non-fatal Stroke; Percentage of Observed Subjects With Outcome Measure Events During the Trial
timeFrame: Randomization to Day 336 (end-of-trial)
measure: Time From Randomization to Confirmed (Adjudicated) CV-related Death; Percentage of Observed Subjects With Outcome Measure Events During the Trial
timeFrame: Randomization to Day 336 (end-of-trial)
measure: Time From Randomization to the First Confirmed (Adjudicated) Myocardial Infarction; Percentage of Observed Subjects With Outcome Measure Events During the Trial
timeFrame: Randomization to Day 336 (end-of-trial)
measure: Time From Randomization to the First Confirmed (Adjudicated) Stroke; Percentage of Observed Subjects With Outcome Measure Events During the Trial
timeFrame: Randomization to Day 336 (end-of-trial)
measure: Time From Randomization to the First Confirmed (Adjudicated) Unstable Angina Requiring Hospitalization; Percentage of Observed Subjects With Outcome Measure Events During the Trial
timeFrame: Randomization to Day 336 (end-of-trial)
measure: Time From Randomization to Death Due to Any Cause; Percentage of Observed Subjects With Outcome Measure Events During the Trial
timeFrame: Randomization to Day 336 (end-of-trial)
measure: Testosterone Levels at Days 28, 168 and 336 in the Degarelix and Leuprolide Treatment Groups
timeFrame: Days 28, 168 and 336 (end-of-trial)
measure: Time From Randomization to Failure in Progression-free Survival (PFS); Percentage of Observed Subjects With Outcome Measure Events During the Trial
timeFrame: From randomization to end-of-trial for each subject (subjects not censored at Day 336)
measure: Changes From Baseline in International Prostate Symptom Score (IPSS) Total and Quality of Life (QoL) Scores
timeFrame: Baseline to Days 168 and 336 (end-of-trial)
measure: Total Number of CV-related Hospitalization Events Over the Duration of the Trial
timeFrame: First dose of IMP to Day 336 (end-of-trial)
measure: Total Number of Coronary Artery By-pass Grafting (CABG) or Percutaneous Coronary Intervention (PCI) Procedures Over the Duration of the Trial
timeFrame: First dose of IMP to Day 336 (end-of-trial)
measure: Total Number of CV-related Emergency Room (ER) Visit Events Over the Duration of the Trial
timeFrame: First dose of IMP to Day 336 (end-of-trial)
measure: Change in Utility, Based on EuroQol Group 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L)
timeFrame: Baseline to Day 336 (end-of-trial)
measure: Changes From Baseline in Duke Activity Status Index (DASI) Global Score
timeFrame: Baseline to Days 168 and 336 (end-of-trial)
measure: Changes From Baseline in Cardiac Anxiety Questionnaire (CAQ) Global Score and Score Per Domain
timeFrame: Baseline to Days 168 and 336 (end-of-trial)
measure: Number of Subjects With Adverse Events (AEs)
timeFrame: Start of IMP treatment until 3 months after last dosing of IMP
measure: Intensity of AEs
timeFrame: Start of IMP treatment until 3 months after last dosing of IMP
measure: Changes in Vital Signs
timeFrame: Baseline to Day 336 (end-of-trial)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Urology Center of Alabama PC
state: Alabama
city: Tucson
country: United States
facility: Arizona Institute of Urology
state: Arizona
city: Tucson
country: United States
facility: Urological Associates of Southern Arizona
state: Arizona
city: Tucson
country: United States
facility: University of Arizona College of Medicine
state: Arizona
city: Little Rock
country: United States
facility: Urology Associates, PA
state: Arkansas
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center, Inc.
state: California
city: La Mesa
country: United States
facility: San Diego Clinical Trials
state: California
city: Lincoln
country: United States
facility: Clinical Trials Research
state: California
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System
state: California
city: Orange
country: United States
facility: University of California, Irvine Medical Center
state: California
city: Torrance
country: United States
facility: Skyline Urology
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Denver
country: United States
facility: Urology Center of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Urologic Surgeons of Washington
state: District of Columbia
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: San Marcus Research Clinic Inc
state: Florida
city: Pompano Beach
country: United States
facility: Clinical Research Center of Florida
state: Florida
city: Tampa
country: United States
facility: Florida Urology Partners
state: Florida
city: Lake Barrington
country: United States
facility: Comprehensive Urologic Care
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic LLP
state: Illinois
city: Greenwood
country: United States
facility: Urology of Indiana LLC
state: Indiana
city: Jeffersonville
country: United States
facility: First Urology PSC
state: Indiana
city: West Des Moines
country: United States
facility: Iowa Clinic
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute, Inc.
state: Kansas
city: Lenexa
country: United States
facility: Kansas City Urology Care
state: Kansas
city: Shreveport
country: United States
facility: Regional Urology, LLC
state: Louisiana
city: Towson
country: United States
facility: Chesapeake Urology Associates, P.A.
state: Maryland
city: Mount Laurel
country: United States
facility: Delaware Valley Urology LLC Westhampton
state: New Jersey
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: Urology Group of New Mexico PC
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center PRIME
state: New York
city: Elmont
country: United States
facility: Advanced Urology Centers of New York Elmont Division
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Salisbury
country: United States
facility: Veterans Affairs Medical Center-Salisbury, NC
state: North Carolina
city: Dayton
country: United States
facility: Signal Point Clinical Research Center
state: Ohio
city: Middleburg Heights
country: United States
facility: Clinical Research Solutions PC
state: Ohio
city: Bala-Cynwyd
country: United States
facility: Urologic Consultants of Southeaster PA LLP
state: Pennsylvania
city: Lancaster
country: United States
facility: Lancaster Urology
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Chattanooga
country: United States
facility: Erlanger Health System
state: Tennessee
city: Norfolk
country: United States
facility: Urology of Virginia
state: Virginia
city: Burien
country: United States
facility: Seattle Urology Research Center
state: Washington
city: Seattle
country: United States
facility: University of Washington School of Medicine
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Inc.
state: Wisconsin
city: Barrie
country: Canada
facility: The Male Health Centre Euroscope Inc
state: Ontario
city: Brampton
country: Canada
facility: J. Giddens Medicine Professional Corporation
state: Ontario
city: Burlington
country: Canada
facility: G. Kenneth Jansz Medicine Professional Corporation
state: Ontario
city: Kitchener
country: Canada
facility: Urology Associates Urologic Medical Research
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Oakville
country: Canada
facility: Femalemale Health Centres
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Laval
country: Canada
facility: Uro Laval
state: Quebec
city: Montréal
country: Canada
facility: Jewish General Hospital / McGill University
state: Quebec
city: Québec
country: Canada
facility: CHU de Québec -Hôtel-Dieu de Québec
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Pardubice
country: Czechia
facility: Multiscan s.r.o.
city: Plzen
country: Czechia
facility: Urocentrum Plzen
city: Praha
country: Czechia
facility: Fakultni nemocnice v Motole
city: Praha
country: Czechia
facility: Proton Therapy Center Czech s.r.o.
city: Příbram
country: Czechia
facility: Oblastni nemocnice Pribram a.s.
city: Ústí Nad Labem
country: Czechia
facility: Krajska zdravotni a.s. - Masarykova nemocnice v Usti nad Labem o.z.
city: Jyväskylä
country: Finland
facility: Keski-Suomen keskussairaala
city: Tampere
country: Finland
facility: Tampereen yliopistollinen
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin Tripode
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Albert Michallon
city: Libourne
country: France
facility: CH de Libourne- Hopital Robert Boulin
city: Lille
country: France
facility: Hopital Claude Huriez - CHU Lille
city: Lyon
country: France
facility: Hopital Edouard Herriot - CHU Lyon
city: Nantes
country: France
facility: Centre Hospitalier Régional Universitaire de Tours
city: Paris
country: France
facility: Hopital Bichat - Claude Bernard
city: Toulouse
country: France
facility: Clinique Saint Jean Languedoc
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
state: Baden Wuerttemberg
city: Kirchheim Unter Teck
country: Germany
facility: Urologische Gemeinschaftspraxis
state: Baden Wuerttemberg
city: Herzogenaurach
country: Germany
facility: Urologische Gemeinschaftspraxis
state: Bayern
city: Braunschweig
country: Germany
facility: Staedtisches Klinikum Braunschweig GmbH - Standort Salzdahlumer
state: Niedersachsen
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg gGmbH
state: Niedersachsen
city: Moenchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH
state: Nordrhein Westfalen
city: Mülheim
country: Germany
facility: Praxisklinik Urologie Rhein Ruhr
state: Nordrhein Westfalen
city: Halle
country: Germany
facility: Krankenhaus Martha-Maria Halle-Doelau
state: Sachsen Anhalt
city: Lutherstadt Eisleben
country: Germany
facility: Facharztpraxis für Urologie
state: Sachsen Anhalt
city: Dresden
country: Germany
facility: Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt
state: Sachsen
city: Leipzig
country: Germany
facility: Urologie am Nordplatz
state: Sachsen
city: Bonn
country: Germany
facility: Gynaekologisches Zentrum Bonn-Friedensplatz
city: Athens
country: Greece
facility: Central Clinic of Athens
city: Athens
country: Greece
facility: General Hospital of Athens "Alexandra"
city: Athens
country: Greece
facility: T.Y.P.E.T. Hygeias Melathron Hospital
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion
city: Patras
country: Greece
facility: University of Patras Medical School
city: Thessaloníki
country: Greece
facility: General Hospital Papageorgiou
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii
city: Piotrków Trybunalski
country: Poland
facility: Provita Profamilia
city: Wrocław
country: Poland
facility: WroMedica
city: Łódź
country: Poland
facility: DERMED Centrum Medyczne Sp. z o.o.
city: Ekaterinburg
country: Russian Federation
facility: SBHI of Sverdiovsk Region "Sverdiovsk Regional Clinical Hospital #1
city: Moscow
country: Russian Federation
facility: City Clinical Hospital n.a. Botkin
city: Moscow
country: Russian Federation
facility: FSBI "Moscow scientific research oncology institute"
city: Moscow
country: Russian Federation
facility: FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
city: Moscow
country: Russian Federation
facility: SBEI HPE "Moscow State Medical and Dentistry University n.a. A. I. Evdokimov"
city: Nizhniy Novgorod
country: Russian Federation
facility: FBHI Privolzhskiy District Medical Centre FMBA of Russia
city: Novosibirsk
country: Russian Federation
facility: Medical Center Avitsenna
city: Omsk
country: Russian Federation
facility: BHI of Omsk region "Clinical Oncology Dispensary
city: Saint-Petersburg
country: Russian Federation
facility: FFSBI "The Nikiforov Russian Center of Emergency and Radiation Medicine"
city: Bratislava
country: Slovakia
facility: CUIMED s.r.o.
city: Bratislava
country: Slovakia
facility: Urocentrum Bratislava s.r.o.
city: Kosice
country: Slovakia
facility: Vychodoslovensky onkologicky ustav, a.s.
city: Košice
country: Slovakia
facility: Nemocnica Kosice-Saca, a.s.
city: Košice
country: Slovakia
facility: Zeleznicna nemocnica Kosice
city: Levice
country: Slovakia
facility: UROCENTRUM LEVICE s.r.o.
city: Liptovský Mikuláš
country: Slovakia
facility: UROAMB s.r.o.
city: Martin
country: Slovakia
facility: Univerzitna nemocnica Martin
city: Nitra
country: Slovakia
facility: Fakultna nemocnica Nitra
city: Nitra
country: Slovakia
facility: UROEXAM, spol. s r.o.
city: Prešov
country: Slovakia
facility: MILAB s.r.o.
city: Rimavska Sobota
country: Slovakia
facility: MIRAMED s.r.o
city: Sala
country: Slovakia
facility: UROCENTRUM SALA s.r.o.
city: Trenčín
country: Slovakia
facility: Privatna Urologicka ambulancia
city: Žilina
country: Slovakia
facility: Fakultna nemocnica s poliklinikou Zilina
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital Department of Urology
state: Western Cape
city: Llanelli
country: United Kingdom
facility: Prince Philip Hospital
state: Carmarthenshire
city: London
country: United Kingdom
facility: Charing Cross Hospital
state: Greater London
city: Scunthorpe
country: United Kingdom
facility: Scunthorpe General Hospital
state: Lincolnshire
city: Chertsey
country: United Kingdom
facility: St Peter's Hospital
state: Surrey
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
state: West Midlands
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital (Wonford)
city: Salford
country: United Kingdom
facility: Salford Royal
Study officials:
affiliation: Ferring Pharmaceuticals
name: Global Clinical Compliance
role: STUDY_DIRECTOR
affiliation: Sidney Kimmel Center for Urologic and Prostate Cancers, Memorial Sloan Kettering Cancer Center
name: Susan Slovin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Cardiovascular Medicine, Duke Clinical Research Institute
name: John Alexander, MD, MHS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lopes RD, Higano CS, Slovin SF, Nelson AJ, Bigelow R, Sorensen PS, Melloni C, Goodman SG, Evans CP, Nilsson J, Bhatt DL, Clarke NW, Olesen TK, Doyle-Olsen BT, Kristensen H, Arney L, Roe MT, Alexander JH; PRONOUNCE Study Investigators. Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial. Circulation. 2021 Oct 19;144(16):1295-1307. doi: 10.1161/CIRCULATIONAHA.121.056810. Epub 2021 Aug 30.
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.
citation: Melloni C, Slovin SF, Blemings A, Goodman SG, Evans CP, Nilsson J, Bhatt DL, Zubovskiy K, Olesen TK, Dugi K, Clarke NW, Higano CS, Roe MT; PRONOUNCE Investigators. Cardiovascular Safety of Degarelix Versus Leuprolide for Advanced Prostate Cancer: The PRONOUNCE Trial Study Design. JACC CardioOncol. 2020 Mar 17;2(1):70-81. doi: 10.1016/j.jaccao.2020.01.004. eCollection 2020 Mar.