Prostate Cancer
Conditions
Brief summary
A phase 3, open-label, parallel group, one year trial comparing the efficacy and safety of degarelix 3-month depot with the established therapy goserelin acetate 3-month implant in patients with prostate cancer.
Interventions
DRUGDegarelix
The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).
DRUGGoserelin acetate
The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years or older. * Has a histological confirmed prostate cancer Gleason graded). * Has a screening testosterone above 2.2 ng/mL. * Rising prostate-specific antigen (PSA). * Has Eastern Cooperative Oncology Group (ECOG) score of ≤ 2. * Has a life expectancy of at least one year.
Exclusion criteria
* Current or previous hormone therapy. * Has received therapy with finasteride and dutasteride within 12 weeks and 25 weeks, respectively, prior to screening. * Has a history of severe untreated asthma, anaphylactic reactions, or severe urticaria and/or angioedema. * Has a heart insufficiency. * 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 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 received an investigational drug within the last 28 days before the Screening Visit or longer if considered to possibly influencing the outcome of the current trial. * Is candidate for curative therapy, i.e. radical prostatectomy or radiotherapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) With Degarelix | From Day 28 to Day 364 | This co-primary outcome measure was used to demonstrate that degarelix is effective with respect to achieving and maintaining testosterone suppression to castrate levels, evaluated as the proportion of patients with testosterone suppression ≤0.5 ng/mL from Day 28 to Day 364. |
| Difference in Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) Between Degarelix and Goserelin | Day 3 to Day 364 | This co-primary outcome measure was used to establish non-inferiority of degarelix as compared to goserelin with regard to achieving and maintaining testosterone suppression at castrate levels (≤0.5 ng/mL) from Day 3 to Day 364, using a non-inferiority margin of 5 percentage points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Levels of Testosterone Over Time | Baseline and after 1, 2, 3, 6 and 13 months | Median testosterone levels are presented as absolute values at Baseline (in Baseline measures) and after 1, 2, 3, 6 and 13 months (below). One treatment month equals 28 days. |
| Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time | Baseline and after 1, 2, 3, 6 and 13 months | Serum PSA levels are presented as mean percent change from Baseline (in Baseline measures) after 1, 2, 3, 6 and 13 months. One treatment month equals 28 days. |
| Change in Health-related Quality of Life (HRQoL), as Measured by Short Form-36 (SF-36) Score at Month 10 and Month 13 Compared to Baseline | At baseline, 10 months and 13 months | The SF-36 is a multi-purpose, short-form health survey with only 36 questions and with a minimum score of 0 and a maximum score of 100. The higher score the better health. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index. The SF-36 has proven useful in surveys of general and specific populations, comparing the relative burden of diseases, and in differentiating the health benefits produced by a wide range of different treatments. |
| Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline | At baseline, 1 month, 4 months, 7 months and 13 months | IPSS is used to assess severity of lower urinary tract symptoms and to monitor the progress of symptoms once treatment has been initiated. It contains 7 questions regarding incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Each question is assigned a score of 0-5 (i.e. the minimum total score is 0 and the maximum is 35). A score of 0 corresponds to a response of not at all for the first six symptoms and none for nocturia, and a score of 5 corresponds to a response of almost always for the first six symptoms and 5 times or more for nocturia. |
Countries
Belgium, Canada, Czechia, Finland, Germany, Hungary, Mexico, Netherlands, Poland, Romania, Russia, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Subjects who met the eligibility criteria were randomized to degarelix or goserelin acetate treatment in a 2:1-ratio. 859 subjects were randomized but 11 subjects did not receive any treatment.
Participants by arm
| Arm | Count |
|---|---|
| Degarelix 240 mg/480 mg Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations). | 565 |
| Goserelin Acetate Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants). | 282 |
| Total | 847 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 41 | 14 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Miscellaneous reasons | 18 | 3 |
| Overall Study | Physician Decision | 5 | 2 |
| Overall Study | Protocol Violation | 16 | 8 |
| Overall Study | Withdrawal by Subject | 28 | 15 |
Baseline characteristics
| Characteristic | Goserelin Acetate | Total | Degarelix 240 mg/480 mg |
|---|---|---|---|
| Age, Continuous | 71.1 years STANDARD_DEVIATION 7.9 | 71.6 years STANDARD_DEVIATION 8.2 | 71.9 years STANDARD_DEVIATION 8.3 |
| Baseline Short Form-36 (SF-36) Total Scores | 50.2 units on a scale STANDARD_DEVIATION 11.4 | 49.9 units on a scale STANDARD_DEVIATION 11.4 | 49.7 units on a scale STANDARD_DEVIATION 11.5 |
| Baseline Total International Prostate Symptom Scores (IPSS) | 11.6 units on a scale STANDARD_DEVIATION 8.02 | 11.7 units on a scale STANDARD_DEVIATION 7.96 | 11.8 units on a scale STANDARD_DEVIATION 7.93 |
| Median Baseline Serum Prostate-specific Antigen Levels (ng/mL) | 19.1 ng/mL | 19.0 ng/mL | 19.0 ng/mL |
| Median Baseline Serum Testosterone Levels (ng/mL) | 4.62 ng/mL | 4.54 ng/mL | 4.52 ng/mL |
| Race (NIH/OMB) American Indian or Alaska Native | 25 Participants | 70 Participants | 45 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 57 Participants | 41 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 239 Participants | 714 Participants | 475 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 282 Participants | 847 Participants | 565 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 336 / 565 | 125 / 283 |
| serious Total, serious adverse events | 58 / 565 | 33 / 283 |
Outcome results
Primary
Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) With Degarelix
This co-primary outcome measure was used to demonstrate that degarelix is effective with respect to achieving and maintaining testosterone suppression to castrate levels, evaluated as the proportion of patients with testosterone suppression ≤0.5 ng/mL from Day 28 to Day 364.
Time frame: From Day 28 to Day 364
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 240 mg/480 mg | Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) With Degarelix | 90.0 percentage of participants |
Primary
Difference in Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) Between Degarelix and Goserelin
This co-primary outcome measure was used to establish non-inferiority of degarelix as compared to goserelin with regard to achieving and maintaining testosterone suppression at castrate levels (≤0.5 ng/mL) from Day 3 to Day 364, using a non-inferiority margin of 5 percentage points.
Time frame: Day 3 to Day 364
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 240 mg/480 mg | Difference in Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) Between Degarelix and Goserelin | 85.0 percentage of participants |
| Goserelin Acetate | Difference in Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) Between Degarelix and Goserelin | 5.3 percentage of participants |
Comparison: The cumulative probability of testosterone ≤0.5 ng/mL from Day 3 to Day 364 was estimated by the Kaplan-Meier method. Only testosterone measurements taken at scheduled trial visits from Day 3 to Day 364 were included in the analysis. The hypothesis to test was the following: a non-inferiority assessment determined whether degarelix was non-inferior to goserelin with respect to the cumulative probability of testosterone ≤0.5 ng/mL from Day 3 to Day 364.95% CI: [75.6, 83.7]
Secondary
Change in Health-related Quality of Life (HRQoL), as Measured by Short Form-36 (SF-36) Score at Month 10 and Month 13 Compared to Baseline
The SF-36 is a multi-purpose, short-form health survey with only 36 questions and with a minimum score of 0 and a maximum score of 100. The higher score the better health. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index. The SF-36 has proven useful in surveys of general and specific populations, comparing the relative burden of diseases, and in differentiating the health benefits produced by a wide range of different treatments.
Time frame: At baseline, 10 months and 13 months
Population: FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Degarelix 240 mg/480 mg | Change in Health-related Quality of Life (HRQoL), as Measured by Short Form-36 (SF-36) Score at Month 10 and Month 13 Compared to Baseline | Month 10 | 0.52 units on a scale | Standard Deviation 11.1 |
| Degarelix 240 mg/480 mg | Change in Health-related Quality of Life (HRQoL), as Measured by Short Form-36 (SF-36) Score at Month 10 and Month 13 Compared to Baseline | Month 13 | 0.18 units on a scale | Standard Deviation 10.9 |
| Goserelin Acetate | Change in Health-related Quality of Life (HRQoL), as Measured by Short Form-36 (SF-36) Score at Month 10 and Month 13 Compared to Baseline | Month 10 | 0.27 units on a scale | Standard Deviation 10.6 |
| Goserelin Acetate | Change in Health-related Quality of Life (HRQoL), as Measured by Short Form-36 (SF-36) Score at Month 10 and Month 13 Compared to Baseline | Month 13 | -0.87 units on a scale | Standard Deviation 9.76 |
Secondary
Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline
IPSS is used to assess severity of lower urinary tract symptoms and to monitor the progress of symptoms once treatment has been initiated. It contains 7 questions regarding incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Each question is assigned a score of 0-5 (i.e. the minimum total score is 0 and the maximum is 35). A score of 0 corresponds to a response of not at all for the first six symptoms and none for nocturia, and a score of 5 corresponds to a response of almost always for the first six symptoms and 5 times or more for nocturia.
Time frame: At baseline, 1 month, 4 months, 7 months and 13 months
Population: FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Degarelix 240 mg/480 mg | Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline | Month 1 | -1.06 units on a scale | Standard Deviation 6.27 |
| Degarelix 240 mg/480 mg | Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline | Month 4 | -2.31 units on a scale | Standard Deviation 6.65 |
| Degarelix 240 mg/480 mg | Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline | Month 7 | -2.47 units on a scale | Standard Deviation 6.94 |
| Degarelix 240 mg/480 mg | Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline | Month 13 | -2.04 units on a scale | Standard Deviation 7.28 |
| Goserelin Acetate | Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline | Month 13 | -1.52 units on a scale | Standard Deviation 6.25 |
| Goserelin Acetate | Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline | Month 1 | -0.21 units on a scale | Standard Deviation 6.22 |
| Goserelin Acetate | Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline | Month 7 | -2.45 units on a scale | Standard Deviation 6.8 |
| Goserelin Acetate | Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline | Month 4 | -1.74 units on a scale | Standard Deviation 6.16 |
Secondary
Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time
Serum PSA levels are presented as mean percent change from Baseline (in Baseline measures) after 1, 2, 3, 6 and 13 months. One treatment month equals 28 days.
Time frame: Baseline and after 1, 2, 3, 6 and 13 months
Population: FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Degarelix 240 mg/480 mg | Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time | Month 1 | -77 percent change | Standard Deviation 23.7 |
| Degarelix 240 mg/480 mg | Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time | Month 6 | -90 percent change | Standard Deviation 30.5 |
| Degarelix 240 mg/480 mg | Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time | Month 3 | -90 percent change | Standard Deviation 15.4 |
| Degarelix 240 mg/480 mg | Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time | Month 13 | -82 percent change | Standard Deviation 104 |
| Degarelix 240 mg/480 mg | Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time | Month 2 | -89 percent change | Standard Deviation 12.6 |
| Goserelin Acetate | Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time | Month 13 | -77 percent change | Standard Deviation 146 |
| Goserelin Acetate | Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time | Month 1 | -57 percent change | Standard Deviation 45.7 |
| Goserelin Acetate | Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time | Month 2 | -86 percent change | Standard Deviation 18.1 |
| Goserelin Acetate | Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time | Month 3 | -86 percent change | Standard Deviation 58.6 |
| Goserelin Acetate | Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time | Month 6 | -91 percent change | Standard Deviation 18.2 |
Secondary
Serum Levels of Testosterone Over Time
Median testosterone levels are presented as absolute values at Baseline (in Baseline measures) and after 1, 2, 3, 6 and 13 months (below). One treatment month equals 28 days.
Time frame: Baseline and after 1, 2, 3, 6 and 13 months
Population: FAS.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Degarelix 240 mg/480 mg | Serum Levels of Testosterone Over Time | Month 6 | 0.09 ng/mL |
| Degarelix 240 mg/480 mg | Serum Levels of Testosterone Over Time | Month 13 | 0.11 ng/mL |
| Degarelix 240 mg/480 mg | Serum Levels of Testosterone Over Time | Month 1 | 0.10 ng/mL |
| Degarelix 240 mg/480 mg | Serum Levels of Testosterone Over Time | Month 2 | 0.09 ng/mL |
| Degarelix 240 mg/480 mg | Serum Levels of Testosterone Over Time | Month 3 | 0.09 ng/mL |
| Goserelin Acetate | Serum Levels of Testosterone Over Time | Month 3 | 0.09 ng/mL |
| Goserelin Acetate | Serum Levels of Testosterone Over Time | Month 2 | 0.10 ng/mL |
| Goserelin Acetate | Serum Levels of Testosterone Over Time | Month 13 | 0.09 ng/mL |
| Goserelin Acetate | Serum Levels of Testosterone Over Time | Month 6 | 0.09 ng/mL |
| Goserelin Acetate | Serum Levels of Testosterone Over Time | Month 1 | 0.16 ng/mL |