Prostate Cancer
Conditions
Keywords
Prostate Cancer, Androgen ablation therapy
Brief summary
The rationale of the study was to evaluate different degarelix dosing regimens for a three-month interval that was to produce and maintain castration in prostate cancer patients through immediate and prolonged testosterone suppression, and to provide confirmatory evidence of the safety of degarelix.
Interventions
DRUGDegarelix
Drug: Degarelix subcutaneous 240 mg (40 mg/mL) initiation dose, maintenance dose 240 mg (40 mg/mL) at months 1, 3, 6 and 9
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
* Has given written consent before any study-related activity is performed. A study-related activity is defined as any procedure that would not have been performed during the normal management of the patient. * Has a histologically confirmed (Gleason graded) adenocarcinoma of the prostate (all stages) in whom endocrine treatment, except for neoadjuvant hormonal therapy, is indicated. This includes patients with rising PSA after having undergone prostatectomy or radiotherapy with curative intention. * Is a male patient aged 18 years or over. * Has a baseline serum testosterone level above the lower limit of normal range, globally defined as \>2.2 ng/mL. * Has an ECOG (Eastern Cooperative Oncology Group) score of 2. * Has a PSA value of 2 ng/mL. * Has a life expectancy of at least 13 months.
Exclusion criteria
* Has had previous or is currently under hormonal management of prostate cancer (surgical castration or other hormonal manipulation, e.g. GnRH agonists, GnRH antagonists, antiandrogens, oestrogens). However, patients having undergone prostatectomy or radiotherapy with curative intention, neoadjuvant hormonal therapy is accepted for a maximal duration of 6 months. This treatment should have been terminated at least 6 months prior to the Screening Visit. * Is considered to be a candidate for curative therapy, i.e. radical prostatectomy or radiotherapy within 13 months from Screening Visit. * Has a history of, or predisposition to, severe hypersensitivity reactions such as severe asthma (defined as a need for daily treatment with inhalation steroids to control the asthma), anaphylactic reactions, or chronic or recurrent urticaria and/or angioedema. * Has hypersensitivity towards any component of the investigational medicinal product. 5. Has had a cancer disease within the last five years except for prostate cancer and surgically removed basal or squamous cell carcinoma of the skin. * Has a known or suspected hepatic or symptomatic biliary disease. * Has elevated serum ALT level above upper level of normal range or serum total bilirubin level above upper level of normal range as measured by the laboratory at the Screening Visit. * Has other clinically significant laboratory abnormalities, which in the judgment of the investigator would interfere with the patient's participation in this study or evaluation of study results. * Has a clinically significant disorder (other than prostate cancer) or any other condition, including excessive alcohol or drug abuse, which may interfere with study participation or which may affect the conclusion of the study as judged by the investigator. * Has a mental incapacity or language barriers precluding adequate understanding or cooperation. * Has received an investigational drug within the last 28 days preceding Screening Visit or longer if considered by the investigator to possibly influence the outcome of the current study. * Has previously participated in any degarelix study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Testosterone Level <=0.5 ng/mL From Day 28 Until the End of the Study | From Day 28 to 12 or 13 months | Figure in the table give the number of participants with all testosterone values \<=0.5 ng/mL from Day 28 to the end of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Testosterone Level <=0.5 ng/mL After the Dose at Day 28 Until the End of the Study | From after Day 28 to 12 or 13 months | Figures in the table give the number of participants with all testosterone values \<=0.5 ng/mL after the dose at Day 28 to end of study. Thus, the testosterone response after the initial dose is not included in this outcome measure. |
| Number of Participants With Testosterone <=0.5 ng/mL at Day 28 | 28 Days | Figures in the table give number of participants with testosterone \<=0.5 ng/mL 28 days after the initial dose of trial medication. |
| Liver Function Tests | 12 or 13 months | 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. |
| Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | 12 or 13 months | 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. |
Countries
Belgium, Canada, Finland, France, Germany, Netherlands, Romania, Russia, Serbia and Montenegro, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Degarelix 240@40/240@40 (1,3,6,9) 240 mg (40 mg/mL) initiation dose, maintenance dose 240 mg (40 mg/mL) at months 1, 3, 6 and 9. | 150 |
| Degarelix 240@40/240@60 (1,3,6,9) 240 mg (40 mg/mL) initiation dose, maintenance dose 240 mg (60 mg/mL) at months 1, 3, 6 and 9. | 150 |
| Degarelix 240@40/240@60 (1,4,7,10) 240 mg (40 mg/mL) initiation dose, maintenance dose 240 mg (60 mg/mL) at months 1, 4, 7 and 10. | 147 |
| Total | 447 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Abnormal Echocardiogram | 0 | 0 | 1 |
| Overall Study | Adverse Event | 16 | 10 | 7 |
| Overall Study | Did not Fulfil Eligibility Criteria | 1 | 1 | 3 |
| Overall Study | Disease Progression | 3 | 4 | 3 |
| Overall Study | Dosing Error | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 | 1 |
| Overall Study | Progressive Parkinson's Disease | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 11 | 12 | 8 |
Baseline characteristics
| Characteristic | Degarelix 240@40/240@40 (1,3,6,9) | Degarelix 240@40/240@60 (1,3,6,9) | Degarelix 240@40/240@60 (1,4,7,10) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 129 Participants | 131 Participants | 127 Participants | 387 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 19 Participants | 20 Participants | 60 Participants |
| Age Continuous | 75 years | 75 years | 75 years | 75 years |
| Body Mass Index | 25.9 kilogram per square meter STANDARD_DEVIATION 4.25 | 26.3 kilogram per square meter STANDARD_DEVIATION 4.42 | 26.0 kilogram per square meter STANDARD_DEVIATION 4.24 | 26.0 kilogram per square meter STANDARD_DEVIATION 4.3 |
| Body Weight | 78.5 kilogram STANDARD_DEVIATION 14.6 | 78.4 kilogram STANDARD_DEVIATION 13.9 | 77.4 kilogram STANDARD_DEVIATION 12.9 | 78.1 kilogram STANDARD_DEVIATION 13.8 |
| Curative Intent No | 133 Participants | 128 Participants | 130 Participants | 391 Participants |
| Curative Intent Yes | 17 Participants | 22 Participants | 17 Participants | 56 Participants |
| Gleason Score 2-4 | 16 participants | 9 participants | 15 participants | 40 participants |
| Gleason Score 5-6 | 52 participants | 43 participants | 61 participants | 156 participants |
| Gleason Score 7-10 | 82 participants | 97 participants | 70 participants | 249 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 15 Participants | 8 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 141 Participants | 131 Participants | 136 Participants | 408 Participants |
| Serum Prostate Specific Antigen Levels | 13.8 nanogram per milliliter | 16.6 nanogram per milliliter | 15.6 nanogram per milliliter | 15.6 nanogram per milliliter |
| Serum Testosterone Levels | 4.43 nanogram per milliliter | 4.00 nanogram per milliliter | 4.07 nanogram per milliliter | 4.23 nanogram per milliliter |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 150 Participants | 150 Participants | 147 Participants | 447 Participants |
| Stage of Prostate Cancer Localized | 56 participants | 62 participants | 66 participants | 184 participants |
| Stage of Prostate Cancer Locally advanced | 40 participants | 31 participants | 34 participants | 105 participants |
| Stage of Prostate Cancer Metastatic | 28 participants | 30 participants | 26 participants | 84 participants |
| Stage of Prostate Cancer Not classifiable | 26 participants | 27 participants | 21 participants | 74 participants |
| Time Since Prostate Cancer Diagnosis | 465 days STANDARD_DEVIATION 1041 | 388 days STANDARD_DEVIATION 968 | 346 days STANDARD_DEVIATION 738 | 400 days STANDARD_DEVIATION 925 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 117 / 150 | 110 / 150 | 107 / 147 |
| serious Total, serious adverse events | 28 / 150 | 25 / 150 | 19 / 147 |
Outcome results
Primary
Number of Participants With Testosterone Level <=0.5 ng/mL From Day 28 Until the End of the Study
Figure in the table give the number of participants with all testosterone values \<=0.5 ng/mL from Day 28 to the end of the study.
Time frame: From Day 28 to 12 or 13 months
Population: Observed Cases in ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 240@40/240@40 (1,3,6,9) | Number of Participants With Testosterone Level <=0.5 ng/mL From Day 28 Until the End of the Study | 94 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Number of Participants With Testosterone Level <=0.5 ng/mL From Day 28 Until the End of the Study | 101 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Number of Participants With Testosterone Level <=0.5 ng/mL From Day 28 Until the End of the Study | 110 participants |
96.5% CI: [69, 86]
96.5% CI: [71, 87]
96.5% CI: [77, 91]
p-value: 0.3022Mantel Haenszel
p-value: 0.7797Mantel Haenszel
p-value: 0.1557Mantel Haenszel
p-value: 0.2208Mantel Haenszel
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: 12 or 13 months
Population: ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Degarelix 240@40/240@40 (1,3,6,9) | Liver Function Tests | ALAT >3x upper limit of normal (ULN) | 2 participants |
| Degarelix 240@40/240@40 (1,3,6,9) | Liver Function Tests | Abnormal bilirubin | 4 participants |
| Degarelix 240@40/240@40 (1,3,6,9) | Liver Function Tests | Abnormal alanine aminotransferase (ALAT) | 60 participants |
| Degarelix 240@40/240@40 (1,3,6,9) | Liver Function Tests | Abnormal aspartate aminitransferase | 40 participants |
| Degarelix 240@40/240@40 (1,3,6,9) | Liver Function Tests | ALAT >3x ULN, bilirubin 1.5x ULN | 0 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Liver Function Tests | Abnormal bilirubin | 7 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Liver Function Tests | Abnormal alanine aminotransferase (ALAT) | 56 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Liver Function Tests | Abnormal aspartate aminitransferase | 45 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Liver Function Tests | ALAT >3x upper limit of normal (ULN) | 2 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Liver Function Tests | ALAT >3x ULN, bilirubin 1.5x ULN | 0 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Liver Function Tests | ALAT >3x ULN, bilirubin 1.5x ULN | 0 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Liver Function Tests | ALAT >3x upper limit of normal (ULN) | 6 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Liver Function Tests | Abnormal alanine aminotransferase (ALAT) | 57 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Liver Function Tests | Abnormal bilirubin | 2 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Liver Function Tests | Abnormal aspartate aminitransferase | 50 participants |
Secondary
Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline
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.
Time frame: 12 or 13 months
Population: ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Degarelix 240@40/240@40 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Diastolic blood pressure <=50 and decrease >=15 | 4 participants |
| Degarelix 240@40/240@40 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Diastolic blood pressure >=105 and increase >=15 | 5 participants |
| Degarelix 240@40/240@40 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Systolic blood pressure <=90 and decrease >=20 | 1 participants |
| Degarelix 240@40/240@40 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Systolic blood pressure >=180 and increase >=20 | 5 participants |
| Degarelix 240@40/240@40 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Heart rate <=50 and decrease >=15 | 6 participants |
| Degarelix 240@40/240@40 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Heart rate >=120 and increase >=15 | 1 participants |
| Degarelix 240@40/240@40 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Body weight decrease of >=7 percent | 5 participants |
| Degarelix 240@40/240@40 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Body weight increase of >=7 percent | 21 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Systolic blood pressure <=90 and decrease >=20 | 3 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Body weight decrease of >=7 percent | 4 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Systolic blood pressure >=180 and increase >=20 | 10 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Heart rate <=50 and decrease >=15 | 7 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Heart rate >=120 and increase >=15 | 2 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Diastolic blood pressure <=50 and decrease >=15 | 6 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Diastolic blood pressure >=105 and increase >=15 | 7 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Body weight increase of >=7 percent | 19 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Systolic blood pressure <=90 and decrease >=20 | 3 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Diastolic blood pressure >=105 and increase >=15 | 7 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Diastolic blood pressure <=50 and decrease >=15 | 2 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Systolic blood pressure >=180 and increase >=20 | 12 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Body weight decrease of >=7 percent | 0 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Heart rate >=120 and increase >=15 | 0 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Heart rate <=50 and decrease >=15 | 8 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Number of Participants With Markedly Abnormal Change in Vital Signs and Body Weight as Compared to Baseline | Body weight increase of >=7 percent | 17 participants |
Secondary
Number of Participants With Testosterone <=0.5 ng/mL at Day 28
Figures in the table give number of participants with testosterone \<=0.5 ng/mL 28 days after the initial dose of trial medication.
Time frame: 28 Days
Population: Observed Cases in ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 240@40/240@40 (1,3,6,9) | Number of Participants With Testosterone <=0.5 ng/mL at Day 28 | 142 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Number of Participants With Testosterone <=0.5 ng/mL at Day 28 | 143 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Number of Participants With Testosterone <=0.5 ng/mL at Day 28 | 142 participants |
95% CI: [93, 99]
95% CI: [94, 100]
95% CI: [94, 100]
Secondary
Number of Participants With Testosterone Level <=0.5 ng/mL After the Dose at Day 28 Until the End of the Study
Figures in the table give the number of participants with all testosterone values \<=0.5 ng/mL after the dose at Day 28 to end of study. Thus, the testosterone response after the initial dose is not included in this outcome measure.
Time frame: From after Day 28 to 12 or 13 months
Population: Observed Cases in ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 240@40/240@40 (1,3,6,9) | Number of Participants With Testosterone Level <=0.5 ng/mL After the Dose at Day 28 Until the End of the Study | 96 participants |
| Degarelix 240@40/240@60 (1,3,6,9) | Number of Participants With Testosterone Level <=0.5 ng/mL After the Dose at Day 28 Until the End of the Study | 101 participants |
| Degarelix 240@40/240@60 (1,4,7,10) | Number of Participants With Testosterone Level <=0.5 ng/mL After the Dose at Day 28 Until the End of the Study | 111 participants |
96.5% CI: [72, 88]
96.5% CI: [72, 87]
96.5% CI: [78, 92]
p-value: 0.383Mantel Haenszel
p-value: 0.9587Mantel Haenszel
p-value: 0.2579Mantel Haenszel
p-value: 0.2072Mantel Haenszel