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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Degarelix
* Drug: Goserelin
* Drug: Bicalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has given written informed consent Patient is 18 years or older Patient has histologically confirmed prostate cancer Patient has a serum prostate-specific antigen (PSA) level at screening >2 ng/mL The prostate size is >30 cubic centimetres (cc), measured by TRUS Patient has had a bone-scan within 12 weeks before inclusion Patient must be able to undergo transrectal examinations Patient has an estimated life expectancy of at least 12 months Exclusion Criteria: Any previous treatments for prostate cancer Previous trans-urethral resection of the prostate (TURP) Is not considered a candidate for medical castration Use of urethral catheter Is currently treated with a 5-alpha reductase inhibitor Is currently treated with an alpha-adrenoceptor antagonist Treatment with botulinum toxin A (Botox) Require radiotherapy during the trial History of severe untreated asthma, anaphylactic reactions, or severe urticaria and/or angioedema Hypersensitivity towards any component of the investigational products or excipients Previous history or presence of another malignancy A clinically significant disorder A corrected QT interval over 450 msec Mental incapacity or language barrier precluding adequate understanding or co-operation Receipt of an investigational drug within the last 28 days proceeding screening Previous participation in any degarelix trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Degarelix 240 mg/80 mg<br>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<br>* 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.<br>* Other names: FIRMAGON;|
| Active Comparator: Goserelin (3.6 mg) + bicalutamide (50 mg)<br>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<br>* 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.<br>* Other names: ZOLADEX;Drug: Bicalutamide<br>* 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.<br>* Other names: CASODEX;|

What is the study measuring?
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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 |