Investigation of the Effect of Degarelix in Terms of Prostate Volume Reduction in Prostate Cancer Patients

A Randomised, Parallel-arm, Open-label Trial Comparing Degarelix With Goserelin Plus Anti-androgen Flare Protection (Bicalutamide), in Terms of Volume Reduction of the Prostate in Patients With Prostate Cancer Being Candidates for Medical Castration

This was a Phase 3b clinical study in prostate cancer patients which aimed to compare the current standard therapy of a gonadotrophin releasing hormone (GnRH) agonist, goserelin (3.6 mg; plus anti-androgen flare protection, bicalutamide), to a novel GnRH antagonist, degarelix (240 mg starting dose/80 mg maintenance dose) with respect to mean percentage reduction in prostate volume.

The hypothesis was that degarelix could decrease prostate size at least as effectively as the combination of a GnRH agonist with an anti-androgen for flare protection.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Degarelix; Drug: Goserelin; Drug: Bicalutamide

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brugge, Belgium
    • Hospital St Jan Brugge
  • Bruxelles, Belgium
    • Institut Jules Bordet
  • Leuven, Belgium
    • University Hospitals Leuven
  • Turnhout, Belgium
    • St. Elisabethziekenhuis
• Denmark
  • Aalborg, Denmark
    • Aalborg Sygehus Syd
  • Ballerup, Denmark
    • Herlev Hospital
  • Holstebro, Denmark
    • Regionhospitalet Holstebro
  • Næstved, Denmark
    • Sygehus Syd, Næstved Sygehus
  • Roskilde, Denmark
    • Roskilde Sygehus
  • Århus, Denmark
    • Arhus Universitetshospital, Skejby
• Finland
  • Helsinki, Finland
    • HYKS/kirurgian klin./urologia
  • Kuopio, Finland
    • KYS/kirurgian klin (Kuopio)
  • Oulu, Finland
    • OYS/kirurgian klinik
  • Tampere, Finland
    • TAYS/kirurgian klinik
• Italy
  • Ancona, Italy
    • Azienda Ospedaliero Universitaria Ospedali Riuniti
  • Avellino, Italy
    • Azienda Ospedaliera S. Giuseppe Moscaaati
  • Bologna, Italy
    • Policlinico S.Orsola Malpighi - Universita' degli Studi di Bologna
  • Brescia, Italy
    • U.O. Di Urologia - Spedali Civili di Brescia
  • Firenze, Italy
    • Clinica Urologica 1 Universita. Firensa
  • Milano, Italy
    • Fondazione IRCCS Istituto Nazionale Tumori
  • Milano, Italy
    • Fondazione IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena
  • Napoli, Italy
    • Azienda Ospedaliera Universitaria Federico II
  • Palermo, Italy
    • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone dell'Universita' degli Studi di Palermo
  • Perugia, Italy
    • Clinica Urologica - Azienda Ospedaliera di Perugia
  • Roma, Italy
    • Azienda Ospedaliera S. Andrea - Universita' la Sapienza di Roma
  • San Giovanni Rotondo, Italy
    • S.C. Di Urologia - IRCCS Ospedale Casa Sollievo della Sofferenza
  • Torino, Italy
    • Azienda Ospedaliero Universitaria S. Giovanni Battista - Molinette
• Norway
  • Moelv, Norway
    • Moelv spesialistsenter
  • Oslo, Norway
    • Aker Universitetssykehus HF
  • Oslo, Norway
    • Det Norske Radiumhospitalet HF
  • Trondheim, Norway
    • St Olavs Hospital HF
• Portugal
  • Amadora, Portugal
    • Hospital Fernando da Fonseca
  • Coimbra, Portugal
    • Hospitais Universidade Coimbra
  • Lisboa, Portugal
    • Centro Hospitalar Lisboa Norte, Hospital Santa Maria
  • Porto, Portugal
    • Hospital S.JOÃO
• Sweden
  • Göteborg, Sweden
    • Investigational Site
  • Göteborg, Sweden
    • SU/Sahlgrenska
  • Helsingborg, Sweden
    • Helsingborgs lasarett
  • Malmö, Sweden
    • Universitetssjukhuset MAS
  • Södertälje, Sweden
    • Södertälje sjukhus
  • Uppsala, Sweden
    • Uppsala/Akademiska sjukhuset
• Turkey
  • Istanbul, Turkey
    • Cerrahpasa Faculty of Medicine, Kocamustafapasa
  • Istanbul, Turkey
    • Istanbul University Faculty of Medicine, ÇAPA
  • Istanbul, Turkey
    • Marmara University Faculty of Medicine, Altunizade
  • Sıhhıye - Ankara, Turkey
    • Ankara University Faculty of Medicine
  • Sıhhıye - Ankara, Turkey
    • Hacettepe University Faculty of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Patient has given written informed consent
2. Patient is 18 years or older
3. Patient has histologically confirmed prostate cancer
4. Patient has a serum prostate-specific antigen (PSA) level at screening >2 ng/mL
5. The prostate size is >30 cubic centimetres (cc), measured by TRUS
6. Patient has had a bone-scan within 12 weeks before inclusion
7. Patient must be able to undergo transrectal examinations
8. Patient has an estimated life expectancy of at least 12 months

Exclusion Criteria:

1. Any previous treatments for prostate cancer
2. Previous trans-urethral resection of the prostate (TURP)
3. Is not considered a candidate for medical castration
4. Use of urethral catheter
5. Is currently treated with a 5-alpha reductase inhibitor
6. Is currently treated with an alpha-adrenoceptor antagonist
7. Treatment with botulinum toxin A (Botox)
8. Require radiotherapy during the trial
9. History of severe untreated asthma, anaphylactic reactions, or severe urticaria and/or angioedema
10. Hypersensitivity towards any component of the investigational products or excipients
11. Previous history or presence of another malignancy
12. A clinically significant disorder
13. A corrected QT interval over 450 msec
14. Mental incapacity or language barrier precluding adequate understanding or co-operation
15. Receipt of an investigational drug within the last 28 days proceeding screening
16. Previous participation in any degarelix trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Degarelix 240 mg/80 mg; The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.	Drug: Degarelix; The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.; Other Names: FE200486; FIRMAGON
Active Comparator: Goserelin (3.6 mg) + bicalutamide (50 mg); Goserelin implants (3.6 mg) were inserted s.c. into the abdominal wall every 28 days. The first dose was administered on Day 0. The second and third doses of goserelin were administered on Days 28 and 56, respectively. On Day 0, participants began once-daily per-oral (p.o.) treatment with bicalutamide (50 mg) as anti-androgen flare protection; this treatment continued for 28 days after the first dose of goserelin.	Drug: Goserelin; Goserelin implants (3.6 mg) were inserted s.c. into the abdominal wall every 28 days. The first dose was administered on Day 0. The second and third doses of goserelin were administered on Days 28 and 56, respectively.; Other Names: ZOLADEX; Drug: Bicalutamide; On Day 0, participants began once-daily per-oral (p.o.) treatment with bicalutamide (50 mg) as anti-androgen flare protection; this treatment continued for 28 days after the first dose of goserelin.; Other Names: CASODEX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 (Full Analysis Set)	TRUS is a method of measuring the size of the prostate.	After treatment of 12 weeks compared to Baseline
Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 (Per Protocol Analysis Set)	TRUS is a method of measuring the size of the prostate.	After treatment of 12 weeks compared to Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Prostate Size Based on TRUS at Week 4 and 8	TRUS is a method of measuring the size of the prostate.	After treatment of 4 and 8 weeks compared to Baseline
Change From Baseline in Total International Prostate Symptom Score (IPSS) at Week 4, 8, and 12	The IPSS is a tool commonly used to assess the severity of lower urinary tract symptoms (LUTS), and to monitor the progress of the disease once treatment has been initiated. The participant completes a questionnaire containing 7 questions regarding incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Each question is assigned a score of 0-5. The total score is then classified according to the following scale: 0 to 7 = mildly symptomatic; 8 to 19 = moderately symptomatic; and 20 to 35 = severely symptomatic.	After treatment of 4, 8, and 12 weeks compared to Baseline
Change in Serum Testosterone Levels During the Study		At 4, 8, and 12 weeks compared to baseline.
Change in Serum Prostate-Specific Antigen (PSA) Levels During the Study		At 4, 8, and 12 weeks compared to baseline.
Change From Baseline in Quality of Life (QoL) Related to Urinary Symptoms at Each Visit	The IPSS questionnaire included an additional single question to assess the participant's QoL in relation to his urinary symptoms. The question was: 'If you were to spend the rest of your life with your urinary condition the way it is now, how would you feel about that?' The possible answers to this question ranged from 'delighted' (a score of '0') to 'terrible' (a score of '6').	After treatment of 4, 8, and 12 weeks compared to Baseline
Change From Baseline in Burden of Urinary Symptoms Based on the Benign Prostatic Hyperplasia Impact Index (BPHII)	The Benign Prostatic Hyperplasia Impact Index (BPHII) is a self-administered questionnaire to measure how much urinary problems affect various domains of health. The higher value the worse are the urinary problems. The minimum possible total value is 0 and the maximum possible total value is 16.	After treatment of 4, 8, and 12 weeks compared to Baseline
Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight	This outcome measure included incidence of markedly abnormal changes in blood pressure (systolic and diastolic), pulse, and body weight. The table presents the number of participants with normal baseline and at least one post-baseline markedly abnormal value.	Baseline to 12 weeks of treatment
Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables	The figures present the number of participants who had abnormal (defined as above upper limit of normal range (ULN)) levels of safety laboratory variables. Only the laboratory variables that had at least one percentage of participants in either group with abnormal value are presented, more variables were included in the study.	Baseline to 12 weeks of treatment

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals

Publications and helpful links

General Publications

• 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.
• Axcrona K, Aaltomaa S, da Silva CM, Ozen H, Damber JE, Tanko LB, Colli E, Klarskov P. Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: degarelix vs goserelin plus bicalutamide. BJU Int. 2012 Dec;110(11):1721-8. doi: 10.1111/j.1464-410X.2012.11107.x. Epub 2012 Apr 13.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: April 17, 2009
• First Submitted That Met QC Criteria: April 17, 2009
• First Posted (Estimate): April 20, 2009

Study Record Updates

• Last Update Posted (Estimate): November 13, 2013
• Last Update Submitted That Met QC Criteria: October 21, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Androgen Antagonists; Goserelin; Bicalutamide
• Other Study ID Numbers: FE200486 CS31; 2008-008604-40 (EudraCT Number)