Neoadjuvant Study Investigating Degarelix in Patients Suffering From Prostate Cancer

Study Overview
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Brief Summary
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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.

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 Prostate Size Reduction in Prostate Cancer Patients of Intermediate-to-high Risk, Who Require Neoadjuvant Hormone Therapy Prior to Radiotherapy (Curative Intent)

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 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.

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>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<br>* 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.<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 14 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 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 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 | 
| 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 |