Degarelix as Second-Line Hormonal Treatment After Prostate-specific Antigen (PSA)-Failure in GnRH Agonist Treated Patients With Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
This was an open-label, multi-centre, uncontrolled, exploratory trial with a duration of 12 months in two cohorts. The trial aimed to investigate Degarelix as a second-line hormonal treatment in Prostate Cancer patients who experienced PSA-Failure following gonadotropin-releasing hormone (GnRH) agonist treatment. The two cohorts differ in Testosterone levels at inclusion.

Official Title
-----------------
An Open-Label, Multi-Centre, Uncontrolled, Exploratory Trial Investigating Degarelix One-Month Dosing Regimen as Second-Line Hormonal Treatment After PSA-Failure in GnRH Agonist Treated Patients With Prostate Cancer

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: degarelix


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient has given written informed consent before any trial-related activity is performed. Patient is 18 years or older. Histologically confirmed prostate cancer. Patient has received GnRH receptor agonist therapy for a duration of at least 12 months (the first dose of GnRH-antagonist is to be administered when the next dose of the GnRH-agonist would have been due). Patient has experienced rising PSA levels although receiving GnRH agonist therapy, defined as two consecutive rises of PSA at least two weeks apart in two 50% increases over the nadir, and at least one PSA value of >2.5 ng/mL within the last six months. Testosterone on castrate level (defined as ≤ 0.5 ng/mL) (cohort 1); Testosterone ≥0.2 ng/mL at inclusion (cohort 2) Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Estimated life expectancy at least 12 months. Exclusion Criteria: Previous history or presence of another malignancy, other than prostate cancer or treated squamous / basal cell carcinoma of the skin, within the last five years. Ongoing GnRH agonist therapy (last dose of previous GnRH agonist must have been received before Visit 1). Any pre-trial secondary hormonal manipulation (including antiandrogens) after PSA increase as described as above and before trial entry. Antiandrogens as part of complete androgen blockade must have been discontinued at least three months before first dose of trial medication. Previous or current treatment with chemotherapy (e.g. estramustine) for prostate cancer. Known hypersensitivity towards any component of the investigational medical product. History of severe uncontrolled asthma, anaphylactic reactions, or severe urticaria and/or angioedema. Known or suspected clinically significant liver and/or biliary disease. Any clinically significant laboratory abnormalities, disorders, or other condition, including alcohol or drug abuse, which may affect the patient's health or the outcome of the trial as judged by the Investigator. Patient has a clinically significant disorder (other than prostate cancer) including, but not limited to, renal, hematological, gastrointestinal, endocrine, cardiac, neurological, or psychiatric disease, and alcohol or drug abuse or any other condition, which may affect the patient's health or the outcome of the trial as judged by the Investigator. Patient has a mental incapacity or language barriers precluding adequate understanding or co-operation. Patient has received an investigational drug within the last 28 days preceding screening visit. Or longer if considered to possibly influencing the outcome of the current trial. Previous participation in any degarelix trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Degarelix<br>Starting dose: 240 mg by subcutaneous (s.c.) injection in the abdomen on Day 0. Maintenance dose: a maximum of 11 doses of 80 mg degarelix were given 28 days apart via single s.c. injections. | Drug: degarelix<br>* Starting dose of 240 mg (40 mg/mL). Maintenance doses of 80 mg (20 mg/mL).<br>* Other names: FE200486;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants' Response in Prostate-Specific Antigen (PSA) Level at Three Months As Compared to Baseline | Response to treatment was defined as: Response (stabilisation or decrease): Difference ≤ +10% of Baseline level No response (increase): Difference > +10% of Baseline level | Day 0 (baseline), 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants' Response in Prostate-Specific Antigen (PSA) Level at One Month As Compared to Baseline | Response to treatment was defined as: Response (stabilisation or decrease): Difference ≤ +10% of Baseline level No response (increase): Difference > +10% of Baseline level. Per protocol, the one month timeframe was only analyzed for cohort 2. | Day 0 (baseline), 1 month | 
| Participants' Response in Prostate-Specific Antigen (PSA) Level at Two Months As Compared to Baseline | Response to treatment was defined as: Response (stabilisation or decrease): Difference ≤ +10% of Baseline level No response (increase): Difference > +10% of Baseline level. Per protocol, the two month timeframe was only analyzed for cohort 2. | Day 0 (baseline), 2 months | 
| Participants at Testosterone Castrate Level Throughout the Study | Participants who had no post-baseline serum testosterone level above castrate level which was <=0.5 ng/mL. | up to month 12 | 
| Change From Baseline in Serum Levels of Testosterone at the Last Visit |  | Day 0 (baseline), up to month 12 (last visit) | 
| Change From Baseline in Serum Levels of Prostate-Specific Antigen (PSA) at Last Visit |  | Day 0 (baseline), up to month 12 (last visit) | 
| Percent Change From Baseline in Serum Levels of Luteinising Hormone (LH) at the Last Visit | LH is measured in IU/L | Day 0 (baseline), up to month 12 (last visit) | 
| Change From Baseline in Serum Levels of Follicle-Stimulating Hormone (FSH) at the Last Visit |  | Day 0 (baseline), up to month 12 (last visit) | 
| Participants at Testosterone Level <=0.2 ng/mL Throughout the Study | Participants in Cohort 2 who had no post-baseline serum testosterone level above 0.2 ng/mL. | up to month 12 | 
| Participants at Testosterone Level <=0.32 ng/mL Throughout the Study | Participants in Cohort 2 who had no post-baseline serum testosterone level above 0.32 ng/mL | up to month 12 | 
| Participants With Prostate-Specific Antigen (PSA) Progression Throughout the Study | Counts of participants who had PSA progression during the study. PSA progression was defined as PSA >+10% of baseline value. | up to month 12 | 
| Kaplan-Meier Estimate for Overall Survival | The overall survival time was defined as number of days from first treatment dose to date of death. If a patient did not die then the patient's data were censored at the date of last visit. | up to month 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hormone refractory prostate cancer, Agonist treatment failure