A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease (PRONOUNCE)
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| ClinicalTrials.gov Identifier: NCT02663908 |
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Recruitment Status :
Completed
First Posted : January 26, 2016
Last Update Posted : October 21, 2021
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Sponsor:
Ferring Pharmaceuticals
Collaborators:
Memorial Sloan Kettering Cancer Center
Duke Clinical Research Institute
Information provided by (Responsible Party):
Ferring Pharmaceuticals
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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 patients with prostate cancer and cardiovascular disease.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Prostate Cancer | Drug: Degarelix Drug: Leuprolide | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 545 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Single (Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | April 19, 2016 |
| Actual Primary Completion Date : | March 29, 2021 |
| Actual Study Completion Date : | March 29, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Prostate cancer
MedlinePlus related topics:
Prostate Cancer
| Arm | Intervention/treatment |
|---|---|
| Experimental: Degarelix |
Drug: Degarelix
Other Name: FIRMAGON |
| Active Comparator: Leuprolide |
Drug: Leuprolide
Other Name: LUPRON DEPOT |
Primary Outcome Measures :
- Time from randomization to the first confirmed (adjudicated) occurrence of the composite Major Adverse Cardiovascular Event (MACE) endpoint [ Time Frame: Up to 336 days ]
Time from randomization (in days) to the first confirmed (adjudicated) occurrence of the composite MACE endpoint are presented.
Composite MACE endpoint was defined as: death due to any cause, non-fatal myocardial infarction or non-fatal stroke.
Secondary Outcome Measures :
- Time from randomization to the first confirmed (adjudicated) occurrence of cardiovascular (CV)-related death, non-fatal myocardial infarction, non-fatal stroke [ Time Frame: Up to 336 days ]Time from randomization (in days) to the first confirmed (adjudicated) occurrence of CV-related death, non-fatal myocardial infarction, non-fatal stroke are presented.
- Time from randomization to confirmed (adjudicated) CV-related death [ Time Frame: Up to 336 days ]Time from randomization (in days) to confirmed (adjudicated) CV-related death is presented.
- Time from randomization to the first confirmed (adjudicated) myocardial infarction [ Time Frame: Up to 336 days ]Time from randomization (in days) to the first confirmed (adjudicated) myocardial infarction is presented.
- Time from randomization to the first confirmed (adjudicated) stroke [ Time Frame: Up to 336 days ]Time from randomization (in days) to the first confirmed (adjudicated) stroke is presented.
- Time from randomization to the first confirmed (adjudicated) unstable angina requiring hospitalization [ Time Frame: Up to 336 days ]Time from randomization (in days) to the first confirmed (adjudicated) unstable angina requiring hospitalization is presented.
- Time from randomization to death due to any cause [ Time Frame: Up to 336 days ]Time from randomization (in days) to death due to any cause is presented.
- Testosterone levels at Days 28, 168 and 336 in the degarelix and leuprolide treatment groups [ Time Frame: At Days 28, 168 and 336 ]Median levels and interquartile ranges for serum testosterone at Days 28, 168 and 336 are presented. Kaplan-Meier estimates of sustained effective (serum testosterone <0.50 ng/mL) and profound (serum testosterone <0.20 ng/mL) castration rates at Day 336 are presented.
- Time from randomization to failure in progression-free survival (PFS) [ Time Frame: Up to 336 days ]Time to PFS 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 prostate-specific antigen (PSA) failure is presented.
- Changes from baseline in International Prostate Symptom Score (IPSS) Total and QoL scores to Days 168 and 336 [ Time Frame: From baseline to Days 168 and 336 ]
Lower urinary tract symptoms were measured with the IPSS Version 1 (standard version; IPSS-1).
The IPSS is a patient-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 the 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 patient's quality of life (QoL) in relation to his urinary symptoms; the 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.
- Total number of CV-related hospitalization events over the duration of the trial [ Time Frame: Up to 336 days ]
- Total number of coronary artery by-pass grafting (CABG) or percutaneous coronary intervention (PCI) procedures over the duration of the trial [ Time Frame: Up to 336 days ]
- Total number of CV-related emergency room (ER) visit events over the duration of the trial [ Time Frame: Up to 336 days ]
- Change in utility, based on EuroQol Group 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L) [ Time Frame: From baseline to Day 336 ]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.
- Changes from baseline in Duke Activity Status Index (DASI) Global score to Days 168 and 336 [ Time Frame: From baseline to Days 168 and 336 ]The DASI is a self-administered instrument developed to measure functional capacity in patients 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.
- Changes from baseline in Cardiac Anxiety Questionnaire (CAQ) Global score and score per domain to Days 168 and 336 [ Time Frame: From baseline to Days 168 and 336 ]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), avoidance (5 items) and attention (5 items). Each question was assigned a score between 0 "never" to 4 "always". A global score and scores per domain was computed with higher score indicating greater cardiac anxiety.
- Number of subjects with adverse events [ Time Frame: Up to 336 days ]Any adverse event occuring in the time interval from initial dosing to 3 months after (1 month=28 days) last dosing of investigational medicinal product were considered treatment-emergent and are presented.
- Intensity of Adverse Events [ Time Frame: Up to 336 days ]The intensity of adverse event was graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.02) 5-point scale and categorized as mild (grade 1), moderate (grade 2), and severe (grades 3, 4, and 5).
- Number of subjects shifting from normal value(s) in vital signs (pulse and blood pressure) at baseline to clinically significant abnormal value [ Time Frame: Up to 336 days ]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.
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| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
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
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): NCT02663908
Locations
Show 133 study locations
Sponsors and Collaborators
Ferring Pharmaceuticals
Memorial Sloan Kettering Cancer Center
Duke Clinical Research Institute
Investigators
| Study Director: | Global Clinical Compliance | Ferring Pharmaceuticals | |
| Principal Investigator: | Susan Slovin, MD | Sidney Kimmel Center for Urologic and Prostate Cancers, Memorial Sloan Kettering Cancer Center | |
| Principal Investigator: | John Alexander, MD, MHS | Division of Cardiovascular Medicine, Duke Clinical Research Institute |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Ferring Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT02663908 |
| Other Study ID Numbers: |
000108 |
| First Posted: | January 26, 2016 Key Record Dates |
| Last Update Posted: | October 21, 2021 |
| Last Verified: | April 2021 |
Additional relevant MeSH terms:
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Prostatic Neoplasms Cardiovascular Diseases Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Prostatic Diseases |
Leuprolide Fertility Agents, Female Fertility Agents Reproductive Control Agents Physiological Effects of Drugs Antineoplastic Agents, Hormonal Antineoplastic Agents |