Prostate Cancer
Conditions
Keywords
Prostate Cancer
Brief summary
The study will have two treatment groups, evaluating two Degarelix doses. First dose is the initial dose followed by a maintenance dose given every three months. The initial dose given to suppress the testosterone level and the three month maintenance dose to maintain the suppressed testosterone level over one year of treatment.
Detailed description
An Open-Label, Multi-Centre, Randomized Parallel-Group Dose-Finding Study, Investigating Efficacy and Safety of Two Degarelix Three-Month Dosing Regimens in Patients with Prostrate Cancer Requiring Androgen Ablation Therapy.
Interventions
DRUGDegarelix
Experimental Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 360 mg SC (by injection under the skin) given after 1, 4, 7, & 10 months.
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
Inclusion /
Exclusion criteria
* Patients, aged 18 years or older, with histologically proven prostate cancer of all stages in whom endocrine treatment is indicated. * Screening testosterone level above the lower limit of normal range, globally defined as \>2.2 ng/mL. * Eastern Cooperative Oncology Group (ECOG) score of ≤2. * Screening prostate-specific antigen (PSA) level ≥ ng/mL.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Probability of Testosterone at Castration Level (≤0.5 ng/mL) From Day 28 Through Day 364 | 1 year | Kaplan-Maier estimates of the cumulative probabilities of testosterone \<=0.5 ng/mL from Day 28 to Day 364. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Probability of Testosterone at Castration Level (≤0.5 ng/mL) From Day 56 Through Day 364 | 1 year | Kaplan-Maier estimates of the cumulative probabilities of testosterone \<=0.5 ng/mL from Day 56 to Day 364. |
| Probability of no PSA Failure | 1 year | Cumulative probability (%) and 95% confidence interval (CI) for completing the study without PSA failure. PSA failure was defined as two consecutive increases of 50%, and at least 5 ng/mL, compared to nadir (lowest level of PSA achieved). |
| Serum Levels of PSA Over Time | 1 year | — |
| Serum Levels of Testosterone Over Time | 1 year | — |
| Serum Levels of Luteinizing Hormone (LH) Over Time | 1 year | — |
| Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Baseline up to 1 year | This outcome measure included incidence of markedly abnormal values in blood pressure (systolic and diastolic), pulse, and body weight during the trial. The table presents the number of participants with a normal baseline value and at least one post-baseline markedly abnormal value. |
| Liver Function Tests | 1 year | The figures present the number of participants who had abnormal (defined as above upper limit of normal range (ULN)) alanine aminotransferase (ALT) levels, aspartate aminotransferase levels, and bilirubin levels plus the number of participants who had ALT increases \>3x ULN and ALT increases \>3x ULN with concurrently increased bilirubin \>1.5 ULN. |
| Serum Levels of Follicle Stimulating Hormone (FSH) Over Time | 1 year | — |
Countries
Canada, Czechia, Hungary, Romania, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Degarelix 240/360 mg Treatment group A: Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 360 mg SC (by injection under the skin) given after 1, 4, 7, & 10 months. | 67 |
| Degarelix 240/480 mg Treatment group B: Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 480 mg SC (by injection under the skin) given after 1, 4, 7, & 10 months. | 66 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 6 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Degarelix 240/480 mg | Total | Degarelix 240/360 mg |
|---|---|---|---|
| Age Continuous | 72.7 years STANDARD_DEVIATION 8.5 | 73.4 years STANDARD_DEVIATION 7.9 | 74.1 years STANDARD_DEVIATION 7.3 |
| Body mass index | 27.4 kilogram per square meter STANDARD_DEVIATION 3.4 | 27.2 kilogram per square meter STANDARD_DEVIATION 3.7 | 27 kilogram per square meter STANDARD_DEVIATION 4 |
| Curative intent No | 60 participants | 120 participants | 60 participants |
| Curative intent Yes | 6 participants | 13 participants | 7 participants |
| Gleason Score 2-4 | 3 participants | 11 participants | 8 participants |
| Gleason Score 5-6 | 24 participants | 43 participants | 19 participants |
| Gleason Score 7-10 | 39 participants | 78 participants | 39 participants |
| Gleason Score Data missing | 0 participants | 1 participants | 1 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 63 Participants | 127 Participants | 64 Participants |
| Serum FSH | 6.9 IU/L | 7.0 IU/L | 8.4 IU/L |
| Serum LH | 4.6 IU/L | 5.3 IU/L | 5.9 IU/L |
| Serum PSA | 18.2 ng/mL | 20.3 ng/mL | 22.9 ng/mL |
| Serum Testosterone | 4.1 ng/mL | 4.1 ng/mL | 4.1 ng/mL |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 66 Participants | 133 Participants | 67 Participants |
| Stage of Prostate Cancer Localized | 19 participants | 45 participants | 26 participants |
| Stage of Prostate Cancer Locally advanced | 22 participants | 39 participants | 17 participants |
| Stage of Prostate Cancer Metastatic | 16 participants | 30 participants | 14 participants |
| Stage of Prostate Cancer Not classifiable | 9 participants | 19 participants | 10 participants |
| Time Since Prostate Cancer Diagnosis | 265 days STANDARD_DEVIATION 499 | 319 days STANDARD_DEVIATION 802 | 370 days STANDARD_DEVIATION 1011 |
| Weight | 82.4 kilogram STANDARD_DEVIATION 13.4 | 80.6 kilogram STANDARD_DEVIATION 13.2 | 78.9 kilogram STANDARD_DEVIATION 12.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 49 / 67 | 53 / 66 |
| serious Total, serious adverse events | 7 / 67 | 11 / 66 |
Outcome results
Primary
Probability of Testosterone at Castration Level (≤0.5 ng/mL) From Day 28 Through Day 364
Kaplan-Maier estimates of the cumulative probabilities of testosterone \<=0.5 ng/mL from Day 28 to Day 364.
Time frame: 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Degarelix 240/360 mg | Probability of Testosterone at Castration Level (≤0.5 ng/mL) From Day 28 Through Day 364 | 89.0 percentage of participants |
| Degarelix 240/480 mg | Probability of Testosterone at Castration Level (≤0.5 ng/mL) From Day 28 Through Day 364 | 93.3 percentage of participants |
Secondary
Liver Function Tests
The figures present the number of participants who had abnormal (defined as above upper limit of normal range (ULN)) alanine aminotransferase (ALT) levels, aspartate aminotransferase levels, and bilirubin levels plus the number of participants who had ALT increases \>3x ULN and ALT increases \>3x ULN with concurrently increased bilirubin \>1.5 ULN.
Time frame: 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Degarelix 240/360 mg | Liver Function Tests | ALAT >3x ULN, bilirubin >1.5x ULN | 0 participants |
| Degarelix 240/360 mg | Liver Function Tests | Abnormal aspartate aminotransferase | 33 participants |
| Degarelix 240/360 mg | Liver Function Tests | ALAT >3x upper limit of normal (ULN) | 1 participants |
| Degarelix 240/360 mg | Liver Function Tests | Abnormal bilirubin | 3 participants |
| Degarelix 240/360 mg | Liver Function Tests | Abnormal alanine aminotransferase (ALAT) | 22 participants |
| Degarelix 240/480 mg | Liver Function Tests | Abnormal bilirubin | 1 participants |
| Degarelix 240/480 mg | Liver Function Tests | ALAT >3x upper limit of normal (ULN) | 3 participants |
| Degarelix 240/480 mg | Liver Function Tests | ALAT >3x ULN, bilirubin >1.5x ULN | 0 participants |
| Degarelix 240/480 mg | Liver Function Tests | Abnormal alanine aminotransferase (ALAT) | 21 participants |
| Degarelix 240/480 mg | Liver Function Tests | Abnormal aspartate aminotransferase | 23 participants |
Secondary
Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight
This outcome measure included incidence of markedly abnormal values in blood pressure (systolic and diastolic), pulse, and body weight during the trial. The table presents the number of participants with a normal baseline value and at least one post-baseline markedly abnormal value.
Time frame: Baseline up to 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Degarelix 240/360 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Body weight decrease of >=7 percent | 6 participants |
| Degarelix 240/360 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Body weight increase of >=7 percent | 8 participants |
| Degarelix 240/360 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Diastolic blood pressure <=50 and decrease >=15 | 0 participants |
| Degarelix 240/360 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Diastolic blood pressure >=105 and increase >=15 | 0 participants |
| Degarelix 240/360 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Systolic blood pressure <=90 and decrease >=20 | 0 participants |
| Degarelix 240/360 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Systolic blood pressure >=180 and increase >=20 | 1 participants |
| Degarelix 240/360 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Heart rate <=50 and decrease >=15 | 0 participants |
| Degarelix 240/360 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Heart rate >=120 and increase >=15 | 0 participants |
| Degarelix 240/480 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Heart rate <=50 and decrease >=15 | 0 participants |
| Degarelix 240/480 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Body weight decrease of >=7 percent | 0 participants |
| Degarelix 240/480 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Systolic blood pressure <=90 and decrease >=20 | 0 participants |
| Degarelix 240/480 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Body weight increase of >=7 percent | 4 participants |
| Degarelix 240/480 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Systolic blood pressure >=180 and increase >=20 | 1 participants |
| Degarelix 240/480 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Diastolic blood pressure <=50 and decrease >=15 | 0 participants |
| Degarelix 240/480 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Heart rate >=120 and increase >=15 | 0 participants |
| Degarelix 240/480 mg | Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | Diastolic blood pressure >=105 and increase >=15 | 0 participants |
Secondary
Probability of no PSA Failure
Cumulative probability (%) and 95% confidence interval (CI) for completing the study without PSA failure. PSA failure was defined as two consecutive increases of 50%, and at least 5 ng/mL, compared to nadir (lowest level of PSA achieved).
Time frame: 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Degarelix 240/360 mg | Probability of no PSA Failure | 93.5 percentage of participants |
| Degarelix 240/480 mg | Probability of no PSA Failure | 94.6 percentage of participants |
Secondary
Probability of Testosterone at Castration Level (≤0.5 ng/mL) From Day 56 Through Day 364
Kaplan-Maier estimates of the cumulative probabilities of testosterone \<=0.5 ng/mL from Day 56 to Day 364.
Time frame: 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Degarelix 240/360 mg | Probability of Testosterone at Castration Level (≤0.5 ng/mL) From Day 56 Through Day 364 | 89.0 percentage of participants |
| Degarelix 240/480 mg | Probability of Testosterone at Castration Level (≤0.5 ng/mL) From Day 56 Through Day 364 | 93.3 percentage of participants |
Secondary
Serum Levels of Follicle Stimulating Hormone (FSH) Over Time
Time frame: 1 year
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Degarelix 240/360 mg | Serum Levels of Follicle Stimulating Hormone (FSH) Over Time | Day 28 | 0.3 IU/L |
| Degarelix 240/360 mg | Serum Levels of Follicle Stimulating Hormone (FSH) Over Time | Day 84 | 0.6 IU/L |
| Degarelix 240/360 mg | Serum Levels of Follicle Stimulating Hormone (FSH) Over Time | Day 364 | 1.6 IU/L |
| Degarelix 240/480 mg | Serum Levels of Follicle Stimulating Hormone (FSH) Over Time | Day 28 | 0.4 IU/L |
| Degarelix 240/480 mg | Serum Levels of Follicle Stimulating Hormone (FSH) Over Time | Day 84 | 0.5 IU/L |
| Degarelix 240/480 mg | Serum Levels of Follicle Stimulating Hormone (FSH) Over Time | Day 364 | 1.0 IU/L |
Secondary
Serum Levels of Luteinizing Hormone (LH) Over Time
Time frame: 1 year
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Degarelix 240/360 mg | Serum Levels of Luteinizing Hormone (LH) Over Time | Day 28 | 0.1 IU/L |
| Degarelix 240/360 mg | Serum Levels of Luteinizing Hormone (LH) Over Time | Day 84 | 0.1 IU/L |
| Degarelix 240/360 mg | Serum Levels of Luteinizing Hormone (LH) Over Time | Day 364 | 0.3 IU/L |
| Degarelix 240/480 mg | Serum Levels of Luteinizing Hormone (LH) Over Time | Day 28 | 0.1 IU/L |
| Degarelix 240/480 mg | Serum Levels of Luteinizing Hormone (LH) Over Time | Day 84 | 0.1 IU/L |
| Degarelix 240/480 mg | Serum Levels of Luteinizing Hormone (LH) Over Time | Day 364 | 0.2 IU/L |
Secondary
Serum Levels of PSA Over Time
Time frame: 1 year
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Degarelix 240/360 mg | Serum Levels of PSA Over Time | Day 84 | 1.2 ng/mL |
| Degarelix 240/360 mg | Serum Levels of PSA Over Time | Day 364 | 0.4 ng/mL |
| Degarelix 240/360 mg | Serum Levels of PSA Over Time | Day 28 | 3.5 ng/mL |
| Degarelix 240/480 mg | Serum Levels of PSA Over Time | Day 28 | 3.1 ng/mL |
| Degarelix 240/480 mg | Serum Levels of PSA Over Time | Day 84 | 1.2 ng/mL |
| Degarelix 240/480 mg | Serum Levels of PSA Over Time | Day 364 | 0.7 ng/mL |
Secondary
Serum Levels of Testosterone Over Time
Time frame: 1 year
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Degarelix 240/360 mg | Serum Levels of Testosterone Over Time | Day 28 | 0.1 ng/mL |
| Degarelix 240/360 mg | Serum Levels of Testosterone Over Time | Day 84 | 0.1 ng/mL |
| Degarelix 240/360 mg | Serum Levels of Testosterone Over Time | Day 364 | 0.1 ng/mL |
| Degarelix 240/480 mg | Serum Levels of Testosterone Over Time | Day 28 | 0.1 ng/mL |
| Degarelix 240/480 mg | Serum Levels of Testosterone Over Time | Day 84 | 0.1 ng/mL |
| Degarelix 240/480 mg | Serum Levels of Testosterone Over Time | Day 364 | 0.1 ng/mL |