A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease

Prostate Cancer Clinical Trial

— PRONOUNCE  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02663908
• Other study ID #: 000108
• Status: Terminated
• Phase: Phase 3
• Start date: April 19, 2016
• Est. completion date: March 29, 2021

Study information

• Verified date: May 2022
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 545
• Est. completion date: March 29, 2021
• Est. primary completion date: March 29, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Degarelix

• Leuprolide

Locations

Country	Name	City	State
Canada	The Male Health Centre Euroscope Inc	Barrie	Ontario
Canada	J. Giddens Medicine Professional Corporation	Brampton	Ontario
Canada	G. Kenneth Jansz Medicine Professional Corporation	Burlington	Ontario
Canada	Urology Associates Urologic Medical Research	Kitchener	Ontario
Canada	Uro Laval	Laval	Quebec
Canada	London Health Sciences Centre	London	Ontario
Canada	Jewish General Hospital / McGill University	Montréal	Quebec
Canada	Femalemale Health Centres	Oakville	Ontario
Canada	CHU de Québec -Hôtel-Dieu de Québec	Québec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice Ostrava	Ostrava
Czechia	Multiscan s.r.o.	Pardubice
Czechia	Urocentrum Plzen	Plzen
Czechia	Fakultni nemocnice v Motole	Praha
Czechia	Proton Therapy Center Czech s.r.o.	Praha
Czechia	Oblastni nemocnice Pribram a.s.	Príbram
Czechia	Krajska zdravotni a.s. - Masarykova nemocnice v Usti nad Labem o.z.	Ústí Nad Labem
Finland	Keski-Suomen keskussairaala	Jyväskylä
Finland	Tampereen yliopistollinen	Tampere
France	Institut Sainte Catherine	Avignon
France	Groupe Hospitalier Pellegrin Tripode	Bordeaux
France	Hôpital Henri Mondor	Créteil
France	CHU de Grenoble - Hôpital Albert Michallon	Grenoble
France	CH de Libourne- Hopital Robert Boulin	Libourne
France	Hopital Claude Huriez - CHU Lille	Lille
France	Hopital Edouard Herriot - CHU Lyon	Lyon
France	Centre Hospitalier Régional Universitaire de Tours	Nantes
France	Hopital Bichat - Claude Bernard	Paris
France	Clinique Saint Jean Languedoc	Toulouse
Germany	Gynaekologisches Zentrum Bonn-Friedensplatz	Bonn
Germany	Staedtisches Klinikum Braunschweig GmbH - Standort Salzdahlumer	Braunschweig	Niedersachsen
Germany	Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt	Dresden	Sachsen
Germany	Universitaetsklinikum Freiburg	Freiburg	Baden Wuerttemberg
Germany	Krankenhaus Martha-Maria Halle-Doelau	Halle	Sachsen Anhalt
Germany	Urologische Gemeinschaftspraxis	Herzogenaurach	Bayern
Germany	Urologische Gemeinschaftspraxis	Kirchheim Unter Teck	Baden Wuerttemberg
Germany	Urologie am Nordplatz	Leipzig	Sachsen
Germany	Facharztpraxis für Urologie	Lutherstadt Eisleben	Sachsen Anhalt
Germany	Kliniken Maria Hilf GmbH	Moenchengladbach	Nordrhein Westfalen
Germany	Praxisklinik Urologie Rhein Ruhr	Mülheim	Nordrhein Westfalen
Germany	Klinikum Oldenburg gGmbH	Oldenburg	Niedersachsen
Greece	Central Clinic of Athens	Athens
Greece	General Hospital of Athens "Alexandra"	Athens
Greece	T.Y.P.E.T. Hygeias Melathron Hospital	Athens
Greece	University General Hospital of Heraklion	Heraklion
Greece	University of Patras Medical School	Patras
Greece	General Hospital Papageorgiou	Thessaloníki
Poland	Swietokrzyskie Centrum Onkologii	Kielce
Poland	DERMED Centrum Medyczne Sp. z o.o.	Lódz
Poland	Provita Profamilia	Piotrków Trybunalski
Poland	WroMedica	Wroclaw
Russian Federation	SBHI of Sverdiovsk Region "Sverdiovsk Regional Clinical Hospital #1	Ekaterinburg
Russian Federation	City Clinical Hospital n.a. Botkin	Moscow
Russian Federation	FSBI "Moscow scientific research oncology institute"	Moscow
Russian Federation	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"	Moscow
Russian Federation	SBEI HPE "Moscow State Medical and Dentistry University n.a. A. I. Evdokimov"	Moscow
Russian Federation	FBHI Privolzhskiy District Medical Centre FMBA of Russia	Nizhniy Novgorod
Russian Federation	Medical Center Avitsenna	Novosibirsk
Russian Federation	BHI of Omsk region "Clinical Oncology Dispensary	Omsk
Russian Federation	FFSBI "The Nikiforov Russian Center of Emergency and Radiation Medicine"	Saint-Petersburg
Slovakia	Fakultna nemocnica s poliklinikou Zilina	Žilina
Slovakia	CUIMED s.r.o.	Bratislava
Slovakia	Urocentrum Bratislava s.r.o.	Bratislava
Slovakia	Nemocnica Kosice-Saca, a.s.	Košice
Slovakia	Zeleznicna nemocnica Kosice	Košice
Slovakia	Vychodoslovensky onkologicky ustav, a.s.	Kosice
Slovakia	UROCENTRUM LEVICE s.r.o.	Levice
Slovakia	UROAMB s.r.o.	Liptovský Mikuláš
Slovakia	Univerzitna nemocnica Martin	Martin
Slovakia	Fakultna nemocnica Nitra	Nitra
Slovakia	UROEXAM, spol. s r.o.	Nitra
Slovakia	MILAB s.r.o.	Prešov
Slovakia	MIRAMED s.r.o	Rimavska Sobota
Slovakia	UROCENTRUM SALA s.r.o.	Sala
Slovakia	Privatna Urologicka ambulancia	Trencín
South Africa	Groote Schuur Hospital Department of Urology	Cape Town	Western Cape
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	St Peter's Hospital	Chertsey	Surrey
United Kingdom	Royal Devon and Exeter Hospital (Wonford)	Exeter
United Kingdom	Prince Philip Hospital	Llanelli	Carmarthenshire
United Kingdom	Charing Cross Hospital	London	Greater London
United Kingdom	Salford Royal	Salford
United Kingdom	Scunthorpe General Hospital	Scunthorpe	Lincolnshire
United Kingdom	Royal Hallamshire Hospital	Sheffield	West Midlands
United States	Urology Group of New Mexico PC	Albuquerque	New Mexico
United States	Pacific Cancer Medical Center, Inc.	Anaheim	California
United States	Urologic Consultants of Southeaster PA LLP	Bala-Cynwyd	Pennsylvania
United States	Urology Center of Alabama PC	Birmingham	Alabama
United States	Montefiore Medical Center PRIME	Bronx	New York
United States	Seattle Urology Research Center	Burien	Washington
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	Ralph H. Johnson VA Medical Center	Charleston	South Carolina
United States	Erlanger Health System	Chattanooga	Tennessee
United States	Signal Point Clinical Research Center	Dayton	Ohio
United States	Urology Center of Colorado	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Advanced Urology Centers of New York Elmont Division	Elmont	New York
United States	Urology of Indiana LLC	Greenwood	Indiana
United States	First Urology PSC	Jeffersonville	Indiana
United States	University of Kansas Medical Center Research Institute, Inc.	Kansas City	Kansas
United States	San Diego Clinical Trials	La Mesa	California
United States	Comprehensive Urologic Care	Lake Barrington	Illinois
United States	Lancaster Urology	Lancaster	Pennsylvania
United States	Kansas City Urology Care	Lenexa	Kansas
United States	Clinical Trials Research	Lincoln	California
United States	Urology Associates, PA	Little Rock	Arkansas
United States	VA Greater Los Angeles Healthcare System	Los Angeles	California
United States	San Marcus Research Clinic Inc	Miami	Florida
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Clinical Research Solutions PC	Middleburg Heights	Ohio
United States	Medical College of Wisconsin, Inc.	Milwaukee	Wisconsin
United States	Delaware Valley Urology LLC Westhampton	Mount Laurel	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Urology of Virginia	Norfolk	Virginia
United States	University of California, Irvine Medical Center	Orange	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Clinical Research Center of Florida	Pompano Beach	Florida
United States	Veterans Affairs Medical Center-Salisbury, NC	Salisbury	North Carolina
United States	University of Washington School of Medicine	Seattle	Washington
United States	Regional Urology, LLC	Shreveport	Louisiana
United States	Springfield Clinic LLP	Springfield	Illinois
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Florida Urology Partners	Tampa	Florida
United States	Holy Name Medical Center	Teaneck	New Jersey
United States	Skyline Urology	Torrance	California
United States	Chesapeake Urology Associates, P.A.	Towson	Maryland
United States	Arizona Institute of Urology	Tucson	Arizona
United States	University of Arizona College of Medicine	Tucson	Arizona
United States	Urological Associates of Southern Arizona	Tucson	Arizona
United States	Urologic Surgeons of Washington	Washington	District of Columbia
United States	Iowa Clinic	West Des Moines	Iowa
United States	Innovative Clinical Research Institute	Whittier	California

Sponsors (3)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals	Duke Clinical Research Institute, Memorial Sloan Kettering Cancer Center

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Finland,  France,  Germany,  Greece,  Poland,  Russian Federation,  Slovakia,  South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Composite MACE endpoint was defined as: death due to any cause, non-fatal myocardial infarction or non-fatal stroke.; Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) occurrence of composite MACE over time. Percentage of observed subjects with outcome measure events during the trial are reported.; Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.	Randomization to Day 336 (end-of-trial)
Secondary	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	Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict confirmed (adjudicated) occurrence of CV-related death, non-fatal myocardial infarction or non-fatal stroke. Percentage of observed subjects with outcome measure events during the trial are reported.; Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.	Randomization to Day 336 (end-of-trial)
Secondary	Time From Randomization to Confirmed (Adjudicated) CV-related Death; Percentage of Observed Subjects With Outcome Measure Events During the Trial	Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict confirmed (adjudicated) CV-related death. Percentage of observed subjects with outcome measure events during the trial are reported. Percentage of observed subjects with outcome measure events during the trial are reported.; Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.	Randomization to Day 336 (end-of-trial)
Secondary	Time From Randomization to the First Confirmed (Adjudicated) Myocardial Infarction; Percentage of Observed Subjects With Outcome Measure Events During the Trial	Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) myocardial infarction. Percentage of observed subjects with outcome measure events during the trial are reported.; Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.	Randomization to Day 336 (end-of-trial)
Secondary	Time From Randomization to the First Confirmed (Adjudicated) Stroke; Percentage of Observed Subjects With Outcome Measure Events During the Trial	Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) stroke. Percentage of observed subjects with outcome measure events during the trial are reported.; Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.	Randomization to Day 336 (end-of-trial)
Secondary	Time From Randomization to the First Confirmed (Adjudicated) Unstable Angina Requiring Hospitalization; Percentage of Observed Subjects With Outcome Measure Events During the Trial	Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) unstable angina requiring hospitalization. Percentage of observed subjects with outcome measure events during the trial are reported.; Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.	Randomization to Day 336 (end-of-trial)
Secondary	Time From Randomization to Death Due to Any Cause; Percentage of Observed Subjects With Outcome Measure Events During the Trial	Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict death due to any cause. Percentage of observed subjects with outcome measure events during the trial are reported.; Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.	Randomization to Day 336 (end-of-trial)
Secondary	Testosterone Levels at Days 28, 168 and 336 in the Degarelix and Leuprolide Treatment Groups	Median levels and interquartile ranges for serum testosterone at Days 28, 168, and 336 are presented.	Days 28, 168 and 336 (end-of-trial)
Secondary	Time From Randomization to Failure in Progression-free Survival (PFS); Percentage of Observed Subjects With Outcome Measure Events During the Trial	Time to failure in PFS was defined as the time, measured in days, from randomization to the first occurrence of either death, radiographic disease progression, introduction of additional prostate cancer therapies for progression, or PSA failure.; Subjects who discontinued treatment with IMP or withdrew from the trial were censored at the time of discontinuation/withdrawal.; Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict failure in PFS. Percentage of observed subjects with outcome measure events during the trial are reported.	From randomization to end-of-trial for each subject (subjects not censored at Day 336)
Secondary	Changes From Baseline in International Prostate Symptom Score (IPSS) Total and Quality of Life (QoL) Scores	Lower urinary tract symptoms were measured with the IPSS Version 1 (IPSS-1). The IPSS is a subject-administered questionnaire containing seven items to evaluate symptoms of urinary obstruction (incomplete emptying, frequency, intermittency, urgency, weak stream, straining, nocturia) over the preceding week. Each urinary symptom question was assigned points from 0 to 5 indicating increasing severity of the particular symptom. The total IPSS-1 score was then calculated as summation over the responses for all 7 questions. The total IPSS-1 score was transformed to a scale from 0 (lowest score) to 100 (highest score). Higher scores reflect higher severity of symptoms. The IPSS-1 included an additional single question to assess a subject's QoL in relation to his urinary symptoms; response to this question was analyzed separately and was not included in the total IPSS score. The score was similarly scaled from 0 to 100.; Change from baseline in IPSS Total and QoL scores are presented.	Baseline to Days 168 and 336 (end-of-trial)
Secondary	Total Number of CV-related Hospitalization Events Over the Duration of the Trial	The total number of CV-related hospitalizations over the duration of the trial was defined as the number of hospitalizations due to CV-related adverse events, observed from the first exposure to IMP up until Day 336 for each subject.	First dose of IMP to Day 336 (end-of-trial)
Secondary	Total Number of Coronary Artery By-pass Grafting (CABG) or Percutaneous Coronary Intervention (PCI) Procedures Over the Duration of the Trial	The total number of CABG or PCI procedures observed for each subject over the duration of the trial	First dose of IMP to Day 336 (end-of-trial)
Secondary	Total Number of CV-related Emergency Room (ER) Visit Events Over the Duration of the Trial	CV-related ER visit events (that did not lead to hospitalization) was observed from the first exposure to IMP up until Day 336 for each subject.	First dose of IMP to Day 336 (end-of-trial)
Secondary	Change in Utility, Based on EuroQol Group 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L)	The EQ-5D-5L essentially consists of 2 systems - the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ VAS is an overall estimation of the present health status. The results from the EQ-5D-5L questionnaire were converted into quality adjusted life year (QALY) units.; The QALY is estimated by combining the value of life (utility value) and length of life. Quality adjusted life years are based on a principle assuming that a year of life lived in perfect health is worth 1 QALY and that a year of life lived in a state of less than perfect health is worth less than 1.	Baseline to Day 336 (end-of-trial)
Secondary	Changes From Baseline in Duke Activity Status Index (DASI) Global Score	The DASI is a self-administered instrument developed to measure functional capacity in subjects with cardiovascular disease (CVD). It contains 12 items referring to the present time, assessing the ability to perform physical tasks in five domains: personal care (1 item), ambulation (4 items), household tasks (4 items), sexual function (1 item) and recreation (2 items). Each question was answered by one of four options: 'yes with no difficulty' / 'yes, but with some difficulty' / 'no, I can't do this' / 'don't do this for other reasons'. A global score was calculated with a higher score indicating a higher functional capacity. The minimum score is 0 and the maximum score is 58.2 points.; Change from baseline in DASI Global score is presented.	Baseline to Days 168 and 336 (end-of-trial)
Secondary	Changes From Baseline in Cardiac Anxiety Questionnaire (CAQ) Global Score and Score Per Domain	The CAQ is a self-administered questionnaire developed to measure heart-focused anxiety in persons with or without heart disease. It contains 18 items referring to the present time assessing cardiac anxiety in three domains: fear (8 items, each item could be scored between 0 "never" to 4 "always", maximum total score 32), avoidance (5 items, each item could be scored between 0 "never" to 4 "always", maximum total score 20) and attention (5 items, each item could be scored between 0 "never" to 4 "always", maximum total score 20). A higher score indicated greater cardiac anxiety and the total score range was between 0 and 72.; Change from baseline in CAQ Global score and score per domain are presented.	Baseline to Days 168 and 336 (end-of-trial)
Secondary	Number of Subjects With Adverse Events (AEs)	Adverse events were recorded from signed informed consent until end-of-trial. Adverse events with onset after start of IMP treatment, and within 3 months after (1 month=28 days) last dosing of IMP, were considered 'treatment-emergent' and are presented for the safety analysis set.	Start of IMP treatment until 3 months after last dosing of IMP
Secondary	Intensity of AEs	The intensity of AE was graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.02) 5-point scale.; AE were categorized as grade 1 Mild (minor; no specific medical intervention; asymptomatic laboratory findings only; marginal clinical relevance), Grade 2 Moderate (minimal intervention: local intervention; non-invasive intervention), Grade 3 Severe (significant symptoms, requiring hospitalization or invasive intervention; transfusion; elective interventional radiological procedure; therapeutic endoscopy or operation), Grade 4 Life-threatening or disabling (complicated by acute, life-threatening metabolic or CV complications such as circulatory failure, hemorrhage, sepsis. Life-threatening physiologic consequences; need for intensive care or emergent invasive procedure; emergent interventional radiological procedure, therapeutic endoscopy or operation) and Grade 5 Death. Events with grades 3, 4 and 5 were categorized as severe.	Start of IMP treatment until 3 months after last dosing of IMP
Secondary	Changes in Vital Signs	Number of subjects shifting from normal value(s) in vital signs (pulse and blood pressure) at baseline to clinically significant abnormal value(s) at end-of-trial are presented.; Note: Only subjects with appropriate baseline and post-baseline data are included in the evaluation.	Baseline to Day 336 (end-of-trial)