Neoadjuvant Study Investigating Degarelix in Patients Suffering From Prostate Cancer

A Randomised, Parallel Arm, Open-label Trial Comparing Degarelix With Goserelin Plus Anti-androgen Flare Protection (Bicalutamide), in Terms of Prostate Size Reduction in Prostate Cancer Patients of Intermediate-to-high Risk, Who Require Neoadjuvant Hormone Therapy Prior to Radiotherapy (Curative Intent)

The purpose of this phase 3B trial was to see how well a new trial drug (degarelix) works in terms of reducing the size of the prostate volume in prostate cancer patients who were scheduled to undergo subsequent radiotherapy for treatment of their prostate cancer. Prior to receiving radiotherapy, it is recommended that patients with intermediate to high risk prostate cancer are pre-treated with hormone therapy (so-called neoadjuvant therapy) which is known to reduce the size of the prostate and thereby decrease the required radiation field and enable a more safe and effective treatment. In this trial, participants were randomly selected (like flipping a coin) to receive either degarelix given alone or a standard hormone therapy (combination of goserelin and bicalutamide. The treatment was given for three months and the prostate size was measured by ultra sound at the beginning and at the end of the trial. The participants were required to come to the clinic for 5 or 6 visits during the three months.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 246
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Besancon, France, 25000
    • Hôpital Jean Minjoz
  • Bordeaux Cedex, France, 33076
    • Institut Bergonie
  • Caen, France, 14000
    • Centre François Baclesse
  • Creteil, France, 94000
    • CHU Henri Mondor
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69008
    • Centre Léon Bérard
  • Marseille, Cedex 5, France, 13385
    • Hôpital de la Timone
  • Montpellier, France, CX5 34298
    • CRLC Val d'Aurelle Oncology Radiotherapy
  • Paris, France, 75000
    • Hôpital Tenon
  • Paris, France, 75010
    • Hôpital Saint Louis, Radiotherapy Departement
  • Perigueux, France, 24000
    • Clinique Francheville
  • Poitiers, France, 86000
    • CHU La Milétrie, Oncology Radiotherapy
  • Saint Herblain Cedex, France
    • Centre de Lutte Contre le Cancer Nantes-Atlantique Centre René Gauducheau
  • Saint Priest en Jarez, France, CX 42271
    • Institut de Cancerologie de La Loire
  • St Brieuc Cedex, France, 22015
    • Clinique Saint Brieuc
  • Strassbourg, France, 67085
    • Centre Paul Strauss
  • Toulon, France, 83100
    • Centre de radiologie Saint Louis
  • Toulouse, France, 31400
    • Clinique du parc
  • Villejuif, France, 94805
    • IGR
• Germany
  • Berlin, Germany, D-12203
    • Charité-Universitätsmedizin, Campus Benjamin Franklin Klinik für Urologie
  • Braunschweig, Germany, D-38126
    • Städtisches Klinikum Braunschweig
  • Dresden, Germany, D-01307
    • Universitätsklinikum Dresden, Klinik und Poliklinik für Urologie
  • Ulm, Germany, D-89081
    • Universitätsklinikum Ulm, Klinik für Strahlentherapie und Radioonkologie
• Greece
  • Alexandroupolis, Greece, 68100
    • General University Hospital of Alexandroupolis
  • Athens, Greece, 15126
    • General Hospital of Athens, "Sismanogleio", University of Athens, Marouse
  • Loannina, Greece, 45110
    • University General Hospital of Loannina, Medical School
  • Patras, Greece, 26504
    • University General Hospital of Patras
• Netherlands
  • Dordrecht, Netherlands, 3318 AT
    • Albert Schweitzer Ziekenhuis, Ioc., Dordwijk
  • Gouda, Netherlands, 2803 HH
    • Groene Hart Ziekenhuis, urology
  • Rotterdam, Netherlands, 3045 PM
    • Franciscus Gasthuis, Dept. urology
  • Rotterdam, Netherlands, 3078HT
    • Maastad Ziekenhuis, Ioc. Clara
  • Schiedam, Netherlands, 3118 JH
    • Vlietland Ziekenhuis, Dept. urology
  • Tilburg, Netherlands, 5000 LC
    • St. Elisabeth Ziekenhuis Tilburg
• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d´Hebron
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Valencia, Spain, 46009
    • Fundación IVO
• United Kingdom
  • Bath, United Kingdom, BA1 3NG
    • Oncology Royal United Hospital Bath NHS Trust
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital, Oncology Centre
  • Leeds, United Kingdom, LS9 7TF
    • St. James' University Hospital
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS, Foundation Trust
  • London, United Kingdom, W6 8FR
    • Charing Cross Hospital
  • Newcastle upon Tyne, United Kingdom, NE4 6BE
    • Northern Centre for Cancer Treatment, Newcastle General Hospital
  • Southhampton, United Kingdom, SO16 6YD
    • Southhampton General Hospital, Cancer Care Directorate, Southhampton Oncology Centre
  • Whitchurch, United Kingdom, CF14 2TL
    • Velindre Hospital, Cardiff University
  • Kent
    • Maidstone, Kent, United Kingdom, ME16 9QQ
      • Kent Oncology Centre Maidstone Hospital
  • Middlesex
    • Northwood, Middlesex, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Center
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Alabama Research Center
    • Homewood, Alabama, United States, 35209
      • Urology Centers of Alabama
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Urological Association
  • Arizona
    • Tuscon, Arizona, United States, 85712
      • Arizona Urologic Specialists
  • California
    • Lagua Hills, California, United States, 92653
      • Orange County Urology
    • Murrieta, California, United States, 92563
      • Tri-Valley Urology Medical Group
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Connecticut Clinical Research Center
  • Florida
    • Aventura, Florida, United States, 33180
      • South Florida Medical Research
    • Celebration, Florida, United States, 34747
      • DCT -Celebration, LLC dba Discovery Clinical Trials
    • St. Petersburg, Florida, United States, 33710
      • Pinellas Urology Inc.
    • Wellington, Florida, United States, 33449
      • Palm Beach Urology Associates
  • Indiana
    • Bloomington, Indiana, United States, 47403
      • Summit Research Institute
    • Fort Wayne, Indiana, United States, 46825
      • Northeast Indiana Research
  • New Jersey
    • Englewood, New Jersey, United States, 07631
      • Urology Center Research Institute
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Urology Group of New Mexico
  • New York
    • Columbia, New York, United States, 12601
      • Premier Medical Group of Hudson
    • New York, New York, United States, 10016
      • University Urology Associates
  • Tennessee
    • Nashville, Tennessee, United States, 37209
      • Urology Associates
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Urology of Virginia

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:

• Patient has given written informed consent before any trial-related activity is performed.
• Has a confirmed prostate cancer in which this type of treatment is needed.

Exclusion Criteria:

• Previous treatment for prostate cancer
• Previous trans-urethral resection of the prostate
• Patients who are lymph node positive or have other metastatic disease
• Use of urethral catheter
• Current treatment with a 5-alpha reductase inhibitor or α-adrenoceptor antagonist.
• History of severe untreated asthma, anaphylactic reactions, or severe urticaria and/or angioedema.
• Hypersensitivity towards any component of the investigational product
• Other previous cancers within the last five years with the exception of prostate cancer and some types of skin cancer.
• Certain risk factors for abnormal heart rhythms/QT prolongation (corrected QT interval over 450 msec., Torsades de Pointes or use of certain medications with potential risk)
• Clinical disorders other than prostate cancer including but not limited to renal, haematological, gastrointestinal, endocrine, cardiac, neurological, psychiatric disease, alcohol or drug abuse or other conditionals as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

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: Firmagon; FE200486
ACTIVE_COMPARATOR: Goserelin (3.6 mg) + bicalutamide (50 mg); On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.	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 3. The second and third doses of goserelin were administered on Days 31 and 59, 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 14 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 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 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
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
Change From Baseline in Serum Testosterone Levels During the Study		After treatment of 4, 8, and 12 weeks compared to Baseline
Change From Baseline in Serum Prostate-Specific Antigen (PSA) Levels During the Study		After treatment of 4, 8, and 12 weeks compared to Baseline
Change From Baseline in Serum Oestradiol Levels During the Study		After treatment of 4, 8, and 12 weeks compared to Baseline

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.
• Mason M, Maldonado Pijoan X, Steidle C, Guerif S, Wiegel T, van der Meulen E, Bergqvist PB, Khoo V. Neoadjuvant androgen deprivation therapy for prostate volume reduction, lower urinary tract symptom relief and quality of life improvement in men with intermediate- to high-risk prostate cancer: a randomised non-inferiority trial of degarelix versus goserelin plus bicalutamide. Clin Oncol (R Coll Radiol). 2013 Mar;25(3):190-6. doi: 10.1016/j.clon.2012.09.010. Epub 2012 Dec 17.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (ACTUAL): September 1, 2011
• Study Completion (ACTUAL): September 1, 2011

Study Registration Dates

• First Submitted: January 30, 2009
• First Submitted That Met QC Criteria: January 30, 2009
• First Posted (ESTIMATE): February 2, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): October 4, 2012
• Last Update Submitted That Met QC Criteria: September 27, 2012
• Last Verified: September 1, 2012

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 CS30; 2008-005232-33 (EUDRACT_NUMBER)