A Study of Degarelix in Patients With Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study was to see if giving Degarelix every month for 7 months then stop treatment for 7 months (intermittent therapy) would show a reduction of negative effects of androgen deprivation therapy by increasing the quality of life while keeping prostate specific antigen (PSA) levels suppressed.

Detailed Description
-----------------
This was an open-label, randomized, parallel-arm, multicenter study to determine if degarelix intermittent therapy was non-inferior to continuous androgen deprivation therapy (combination of treatment groups receiving continuous degarelix and leuprolide therapy, respectively) in maintaining PSA levels at ≤ 4.0 ng/mL at 14 months. The study consisted of two phases, Phase A and B. During Phase A, patients in the degarelix intermittent and degarelix continuous arms received 7 months of therapy with degarelix one-month depot formulation and patients in the leuprolide continuous arm received leuprolide one-month depot injection (7.5 mg) followed by two 3-month depot (22.5 mg) injections. After 7 months of treatment, patients with a PSA ≤2 ng/mL continued into Phase B. During Phase B, patients in the degarelix intermittent arm had a 7-month off-treatment period. Patients randomized to the degarelix continuous arm and the leuprolide continuous arm continued to receive degarelix or leuprolide depot as in Phase A for the remainder of the 14 months.

Official Title
-----------------
A Randomized, Controlled, Open-Label Study Investigating the Safety and Efficacy of Degarelix Given Intermittently vs Continuous Androgen Deprivation Therapy With Lupron or Degarelix in Patients With Prostate Cancer With Prior Treatment Failure After Localized Treatment

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

Intervention / Treatment
-----------------
* Drug: Degarelix
* Drug: Degarelix
* Drug: Leuprolide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years or older. Raising PSA after prior treatment failure of localized prostate cancer. Has a histological confirmed non-metastatic cancer of the prostate (Gleason graded) based on the most current biopsy. Has a screening testosterone within normal range (≥1.5 ng/mL). Has Eastern Cooperative Oncology Group score of ≤2. Bone scan or CT scan report documenting no evidence of metastasis to the bone or internal organs. Life expectancy of at least 15 months. Exclusion Criteria: Taken hormone therapy in the last 6 months prior to entering this study. Being treated with 5-alpha reductase inhibitor at time of enrolment and remained on a stable dose throughout the trial. Has a history of severe uncontrolled asthma, anaphylactic reactions, or severe urticaria and/or angioedema. Has hypersensitivity towards any component of the study drug. Has a 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. Has abnormal laboratory results which in the judgement of the Investigator would affect the patient's health or the outcome of the trial. Has a clinically significant medical condition (other than prostate cancer) including but not limited to; renal, haematological, 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. Has an intellectual incapacity or language barriers precluding adequate understanding or co-operation. Has received an investigational drug within the last 28 days before the Screening visit or longer if considered to possibly influence the outcome of the current trial. Has received ketoconazole or diflucan in the last 28 days preceding the Screening Visit. Has previously participated in any Degarelix trial. Is part of an ongoing 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DI (Degarelix Intermittent)<br>Patients in this arm received degarelix with a starting dose of 240 mg at a concentration of 40 mg/mL on Day 0 administered subcutaneously (s.c.) into the anterior abdominal wall via two equivalent injections of 120 mg (3 mL) each. Six maintenance doses of degarelix 80 mg per month at a concentration of 20 mg/mL (4 mL) at Days 28 to 168 were administered. During Phase B of the trial, If a patient had Prostate Specific Antigen (PSA) ≥2 ng/mL at any visit, additional doses of degarelix 240 mg followed by 80 mg maintenance dose(s) were administered. | Drug: Degarelix<br>* Degarelix treatment provided for first seven months (one starting dose and six maintenance doses) followed by no treatment for next seven months period.<br>|
| Experimental: DC (Degarelix Continuous)<br>Patients in this arm received degarelix with a starting dose of 240 mg at a concentration of 40 mg/mL administered on Day 0 (Visit 1) s.c. into the anterior abdominal wall via two equivalent injections of 120 mg (3 mL) each. Thirteen maintenance doses of degarelix 80 mg per month at a concentration of 20 mg/mL (4 mL) at Days 28 to 364, administered s.c. into the anterior abdominal wall | Drug: Degarelix<br>* Degarelix treatment provided for complete study period (one starting dose and 13 maintenance doses).<br>|
| Active Comparator: LC (Leuprolide Continuous)<br>Patients in this arm received leuprolide 7.5 mg one-month depot injection on Day 0, administered intramuscular (i.m.) into a large muscle, as per manufacturer's labeling directions. One injection of 22.5 mg leuprolide 3-month depot was administered i.m. as per manufacturer's labeling directions at Day 28 and every 3 months afterwards for 4 additional doses (i.e at Days 112, 196, 280, and 364, respectively). On Investigator's discretion, patients in the arm could take bicalutamide (Casodex®) for a maximum of 28 days to alleviate increased signs and symptoms due to initial upsurge in testosterone levels. | Drug: Leuprolide<br>* Leuprolide treatment for complete study period (one starting dose and 5 maintenance doses of 3-month depot each)<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Serum PSA Levels ≤4.0 ng/mL | Percentage of patients with serum PSA levels ≤4.0 ng/mL at 14 month was presented. | At 14 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Serum PSA Levels | Absolute change from Baseline in serum PSA levels during the study period was measured. | Phase A Visit 1-8 and Phase B Visit 9-15. | 
| Percent Change From Baseline in Serum PSA Levels | Percent change from Baseline in serum PSA levels during the study period was measured. | Phase A Visit 1-8 and Phase B Visit 9-15. | 
| Change From Baseline in Quality of Life as Assessed by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) : Physical Well-being | The FACT-P is a multidimensional, self-report quality of life (QoL) instrument specifically designed for use with prostate cancer patients. It consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Each question is rated on a scale from 0 to 4, and then combined to produce sub-scale scores for each domain, as well as a global QoL score. Physical well-being consist of 7 items and scored on a scale of 0-4 (0=Not at all; 1=A little bit; 2=Somewhat; 3=Quite a bit; 4=Very much). Total score for the physical well-being sub scale ranges from 0 to 28. Higher scores represent better QoL. | During 14 months | 
| Change From Baseline in Quality of Life as Assessed by the FACT-P : Emotional Well-being | The FACT-P is a multidimensional, self-report quality of life (QoL) instrument specifically designed for use with prostate cancer patients. It consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Each question is rated on a scale from 0 to 4, and then combined to produce sub-scale scores for each domain, as well as a global QoL score. Emotional well-being consist of 6 items and scored on a scale of 0-4 (0=Not at all; 1=A little bit; 2=Somewhat; 3=Quite a bit; 4=Very much). Total score for the emotional well-being sub scale ranges from 0 to 24. Higher scores represent better QoL.Higher scores represent better QoL. | During 14 months | 
| Change From Baseline in Quality of Life as Assessed by the FACT-P : Social Well-being | The FACT-P is a multidimensional, self-report quality of life (QoL) instrument specifically designed for use with prostate cancer patients. It consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Each question is rated on a scale from 0 to 4, and then combined to produce sub-scale scores for each domain, as well as a global QoL score. Social well-being consist of 7 items and scored on a scale of 0-4 (0=Not at all; 1=A little bit; 2=Somewhat; 3=Quite a bit; 4=Very much). Total score for the social well-being sub scale ranges from 0 to 28. Higher scores represent better QoL. | During 14 months | 
| Change From Baseline in Quality of Life as Assessed by the FACT-P : Functional Well-being | The FACT-P is a multidimensional, self-report quality of life (QoL) instrument specifically designed for use with prostate cancer patients. It consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Each question is rated on a scale from 0 to 4, and then combined to produce sub-scale scores for each domain, as well as a global QoL score. Functional well-being consist of 7 items and scored on a scale of 0-4 (0=Not at all; 1=A little bit; 2=Somewhat; 3=Quite a bit; 4=Very much). Total score for the functional well-being sub scale ranges from 0 to 28. Higher scores represent better QoL. | During 14 months | 
| Change From Baseline in Quality of Life as Assessed by the FACT-P : Additional Concerns | The FACT-P is a multidimensional, self-report quality of life (QoL) instrument specifically designed for use with prostate cancer patients. It consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Each question is rated on a scale from 0 to 4, and then combined to produce sub-scale scores for each domain, as well as a global QoL score. Additional concerns consist of 12 items and scored on a scale of 0-4 (0=Not at all; 1=A little bit; 2=Somewhat; 3=Quite a bit; 4=Very much). Total score for the additional concerns ranges from 0 to 48. Higher scores represent better QoL. | During 14 months | 
| Change From Baseline in Quality of Life as Assessed by the FACT-P: Total FACT-P Score | The FACT-P is a multidimensional, self-report quality of life (QoL) instrument specifically designed for use with prostate cancer patients. It consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Each question is rated on a scale from 0 to 4, and then combined to produce sub-scale scores for each domain, as well as a global QoL score. Total FACT-P scores ranges from 0 to 156. Higher scores represent better QoL. | During 14 months | 
| Change From Baseline in Sexual Function as Assessed by the Sexual Function Index (SFI): Sexual Drive | The SFI is a multidimensional, self-report instrument specifically designed to evaluate sexual function and satisfaction of men on treatment or with conditions that may affect sexual function. It consists of 11 questions which assess patient function in four domains: Sexual drive, Erection, Ejaculation, and Problem assessment, and a question in regards to overall assessment of sexual function. Sexual drive domain consist of 2 questions and are scored on a scale of 0-4 (0=minimum, 4=maximum). Total score for the sexual drive domain ranges from 0 to 8. A higher scores represent better sexual function. | During 14 months | 
| Change From Baseline in Sexual Function as Assessed by the SFI: Erection | The SFI is a multidimensional, self-report instrument specifically designed to evaluate sexual function and satisfaction of men on treatment or with conditions that may affect sexual function. It consists of 11 questions which assess patient function in four domains: Sexual drive, Erection, Ejaculation, and Problem assessment, and a question in regards to overall assessment of sexual function. Erection domain consist of 3 questions and are scored on a scale of 0-4 (0=minimum, 4=maximum). Total score for the erection domain ranges from 0 to 12. A higher scores represent better sexual function. | During 14 months | 
| Change From Baseline in Sexual Function as Assessed by the SFI: Ejaculation | The SFI is a multidimensional, self-report instrument specifically designed to evaluate sexual function and satisfaction of men on treatment or with conditions that may affect sexual function. It consists of 11 questions which assess patient function in four domains: Sexual drive, Erection, Ejaculation, and Problem assessment, and a question in regards to overall assessment of sexual function. Ejaculation domain consist of 2 questions and are scored on a scale of 0-4 (0=minimum, 4=maximum). Total score for the ejaculation domain ranges from 0 to 8. A higher scores represent better sexual function. | During 14 months | 
| Change From Baseline in Sexual Function as Assessed by the SFI: Problem Assessment | The SFI is a multidimensional, self-report instrument specifically designed to evaluate sexual function and satisfaction of men on treatment or with conditions that may affect sexual function. It consists of 11 questions which assess patient function in four domains: Sexual drive, Erection, Ejaculation, and Problem assessment, and a question in regards to overall assessment of sexual function. Problem assessment domain consist of 2 questions and are scored on a scale of 0-4 (0=minimum, 4=maximum). Total score for the problem assessment domain ranges from 0 to 8. A higher scores represent better sexual function. | During 14 months | 
| Change From Baseline in Sexual Function as Assessed by the SFI: Overall Satisfaction With Sex Life | The SFI is a multidimensional, self-report instrument specifically designed to evaluate sexual function and satisfaction of men on treatment or with conditions that may affect sexual function. It consists of 11 questions which assess patient function in four domains: Sexual drive, Erection, Ejaculation, and Problem assessment, and a question in regards to overall assessment of sexual function. Overall satisfaction domain consist of single question and is scored on a scale of 0-4 (0=minimum, 4=maximum). A higher score represent better sexual function. | During 14 months | 
| Change From Baseline in Sexual Function as Assessed by the SFI: Total SFI Score | The SFI is a multidimensional, self-report instrument specifically designed to evaluate sexual function and satisfaction of men on treatment or with conditions that may affect sexual function. It consists of 11 questions which assess patient function in four domains: Sexual drive, Erection, Ejaculation, and Problem assessment, and a question in regards to overall assessment of sexual function. Total SFI score ranges from 0 to 44. A higher scores represent better sexual function. | During 14 months | 
| Percentage of Subjects With a Serum PSA Level ≤4.0 ng/mL | Percentage of Subjects With a Serum PSA Level ≤4.0 ng/mL was measured during the study period. | At 14 months | 
| Time to Return to Testosterone >0.5 ng/mL Level in the DI Treatment Group | The time to testosterone >0.5 ng/mL level in the DI group was counted from the start of Phase B at Day 196 (i.e. 28 days after last injection of degarelix) | During Phase B | 
| Time to Return to Normal Range (≥1.5 ng/mL) or Baseline Testosterone Level | The time to return to normal range (≥1.5 ng/mL) or Baseline testosterone level in the DI group was counted from the start of Phase B at Day 196 (i.e. 28 days after last injection of degarelix). | During Phase B | 
| Absolute Change From Baseline in Serum Testosterone Levels | Absolute Change From Baseline in Serum Testosterone Levels was measured. | Phase A Visit 1-8 and Phase B Visit 9-15. | 
| Percent Change From Baseline in Serum Testosterone Levels | Percent change from Baseline in serum testosterone levels was measured. | Phase A Visit 1-8 and Phase B Visit 9-15. |