Prostate Cancer
Conditions
Brief summary
A phase III extension trial comparing the efficacy and safety of degarelix 3 month depot with the established therapy Zoladex 3 month implant in patients with prostate cancer.
Detailed description
CS35A was an open-label, multicentre, comparative non-inferiority extension trial to the Phase 3 CS35 trial (NCT00946920). In the main CS35 trial, participants were randomised 2:1 to treatment with degarelix or goserelin, respectively. All participants who completed the main CS35 trial after initiation of the CS35A trial were eligible to enrol into this extension trial, provided that their treatment could continue uninterrupted. Patients entering the CS35A trial continued with the same 3-monthly treatment as they received in CS35 (i.e. degarelix 480 mg or goserelin 10.8 mg). It was intended that patients enrolled in the CS35A trial would receive treatment with degarelix or goserelin at 3-month intervals for a period of 40 months (including 13 months' treatment in CS35). It was, however, decided to prematurely terminate the CS35A trial due to an insufficient number of patients being enrolled. Maximum exposure of treatment was 111 weeks (in both treatment arms). The baseline characteristics are based on the CS35A Full Analysis Set (FAS)defined as all participants who received at least one dose of degarelix or goserelin acetate during CS35A and had at least one efficacy assessment after dosing. All efficacy analyses were performed for the CS35/CS35A FAS defined as all participants who received at least one dose of degarelix or goserelin acetate during CS35 and had at least one efficacy assessment after dosing. All safety analyses were performed for the CS35/CS35A Safety analysis set, which included all patients who received at least one dose of degarelix or goserelin acetate during CS35.
Interventions
DRUGDegarelix
The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. In the main CS35 trial, 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 in the main trial). In the CS35A extension trial, the participants received the same treatment as in the main trial ie the degarelix treated participants continued to receive degarelix 480 mg s.c. treatment every three months.
DRUGGoserelin acetate
The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. In the main CS35 trial, 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 in the main trial). In the CS35A extension trial, the participants received the same treatment as in the main trial ie the goserelin treated participants continued to receive goserelin acetate 10.8 mg s.c. implants every three months.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
NON_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 prior to any trial-related activity is performed. (A trial-related activity is defined as any procedure that would not have been performed during the normal management of the patient). * Has completed the CS35 trial.
Exclusion criteria
* Has been withdrawn from the CS35 trial. * Has had end of trial visit in CS35 prior to approval of the CS35A protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hazard Ratio of Prostate-specific Antigen (PSA) Progression-free Survival (PFS) Failure Rates During 3 Years' Treatment Between Degarelix and Goserelin | From baseline to 3 years | PSA PFS failure is defined as either PSA failure (defined as increase in serum PSA of 50%, and at least 5 ng/mL, compared to nadir, measured on two consecutive occasions at least 2 weeks apart) or death, whichever is first. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no PSA-PFS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hazard Ratio of PSA Failure Rates During 3 Years Treatment Between Degarelix and Goserelin | From baseline to 3 years | PSA failure is defined as increase in serum PSA of 50%, and at least 5 ng/mL, compared to nadir, measured on two consecutive occasions at least 2 weeks apart. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no PSA failure. |
| Hazard Ratio of Testosterone Escape Rates During 3 Years' Treatment Between Degarelix and Goserelin | From baseline to 3 years | Testosterone escape is defined as serum levels \>0.5 ng/mL. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no testosterone escape. |
| Hazard Ratio of the Rates of Introduction of Additional Therapy Related to Prostate Cancer During 3 Years' Treatment Between Degarelix and Goserelin | From baseline to 3 years | Additional therapy related to prostate cancer included radiation, anti-androgens and second-line treatment. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no additional therapy related to prostate cancer. |
| Hazard Ratio of PFS Failure Rates During 3 Years Treatment Between Degarelix and Goserelin | From baseline to 3 years | PFS failure is defined as either PSA failure, introduction of additional therapy related to prostate cancer (radiation, anti-androgens or second-line treatment), or death, whichever is first. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no PFS failure. |
| Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin | Baseline and after 1, 6, 12, 19, and 22 months | Median testosterone levels are presented as absolute values in nanograms per milliliter (ng/mL) at baseline and after 1, 6, 12, 19, and 22 months. One month equals 28 days. After 22 months, only a limited number of samples were analysed. |
| Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin | Baseline and after 1, 6, 12, 19, and 22 months | Median PSA levels are presented as absolute values in nanograms per milliliter (ng/mL) at baseline and after 1, 6, 12, 19, and 22 months. One month equals 28 days. After 22 months, only a limited number of samples were analysed. |
| Hazard Ratio of Mortality Rates During 3 Years' Treatment Between Degarelix and Goserelin | From baseline to 3 years | The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of death. |
Countries
Belgium, Canada, Czechia, Finland, Germany, Hungary, Mexico, Netherlands, Poland, Romania, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
All participants who completed the main CS35 trial after initiation of the CS35A extension trial were eligible to enrol into CS35A.
Pre-assignment details
Participants entering the CS35A trial continued with the same 3-monthly treatment as they received in CS35 (i.e. degarelix 480 mg or goserelin 10.8 mg).
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. In the main CS35 trial, 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 in the main trial). In the CS35A extension trial, the participants received the same treatment as in the main trial ie the degarelix treated participants continued to receive degarelix 480 mg s.c. treatment every three months. | 194 |
| Goserelin Acetate Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. In the main CS35 trial, 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 in the main trial). In the CS35A extension trial, the participants received the same treatment as in the main trial ie the goserelin treated participants continued to receive goserelin acetate 10.8 mg s.c. implants every three months. | 94 |
| Total | 288 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 5 |
| Overall Study | Lost to Follow-up | 6 | 2 |
| Overall Study | Miscellaneous reasons | 8 | 3 |
| Overall Study | Physician Decision | 3 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 2 |
Baseline characteristics
| Characteristic | Degarelix 240 mg/480 mg | Goserelin Acetate | Total |
|---|---|---|---|
| Age, Continuous | 73.1 years STANDARD_DEVIATION 8.4 | 71.3 years STANDARD_DEVIATION 7 | 72.5 years STANDARD_DEVIATION 8 |
| Median Baseline Serum Prostate-specific Antigen Levels | 20.6 ng/mL | 16.6 ng/mL | 18.7 ng/mL |
| Median Baseline Serum Testosterone Levels | 4.41 nanogram per milliliter (ng/mL) | 4.65 nanogram per milliliter (ng/mL) | 4.52 nanogram per milliliter (ng/mL) |
| Race (NIH/OMB) American Indian or Alaska Native | 34 Participants | 21 Participants | 55 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants | 10 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 | 154 Participants | 68 Participants | 222 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 194 Participants | 94 Participants | 288 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 430 / 565 | 197 / 283 |
| serious Total, serious adverse events | 58 / 565 | 33 / 283 |
Outcome results
Primary
Hazard Ratio of Prostate-specific Antigen (PSA) Progression-free Survival (PFS) Failure Rates During 3 Years' Treatment Between Degarelix and Goserelin
PSA PFS failure is defined as either PSA failure (defined as increase in serum PSA of 50%, and at least 5 ng/mL, compared to nadir, measured on two consecutive occasions at least 2 weeks apart) or death, whichever is first. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no PSA-PFS.
Time frame: From baseline to 3 years
Population: CS35 (NCT00946920)/CS35A Full Analysis Set (degarelix n=565; goserelin n=282). The analysis population was pre-specified in the study protocol and statistical analysis plan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 240 mg/480 mg | Hazard Ratio of Prostate-specific Antigen (PSA) Progression-free Survival (PFS) Failure Rates During 3 Years' Treatment Between Degarelix and Goserelin | 75.5 percentage of no PSA-PFS |
| Goserelin Acetate | Hazard Ratio of Prostate-specific Antigen (PSA) Progression-free Survival (PFS) Failure Rates During 3 Years' Treatment Between Degarelix and Goserelin | 75.4 percentage of no PSA-PFS |
Comparison: The hazard ratio of PSA PFS failure rates was estimated using the Cox proportional hazard model with time to PSA PFS failure as dependent and treatment as independent variables and adjusted for baseline PSA category, prostate cancer stage, weight and geographical region. Degarelix was to be considered non-inferior to goserelin if the upper limit of the two-sided 95% confidence interval (CI) of the adjusted hazard ratio was less than or equal to the non-inferiority margin of 1.33.p-value: 0.158995% CI: [0.542, 1.106]Cox proportional hazard model
Secondary
Hazard Ratio of Mortality Rates During 3 Years' Treatment Between Degarelix and Goserelin
The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of death.
Time frame: From baseline to 3 years
Population: CS35 (NCT00946920)/CS35A Full Analysis Set (degarelix n=565; goserelin n=282). The analysis population was pre-specified in the study protocol and statistical analysis plan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 240 mg/480 mg | Hazard Ratio of Mortality Rates During 3 Years' Treatment Between Degarelix and Goserelin | 4.6 percentage of deaths |
| Goserelin Acetate | Hazard Ratio of Mortality Rates During 3 Years' Treatment Between Degarelix and Goserelin | 5.3 percentage of deaths |
Comparison: The hazard ratio was estimated using the Cox proportional hazard model.p-value: 0.221295% CI: [0.259, 1.368]Cox proportional hazard model
Secondary
Hazard Ratio of PFS Failure Rates During 3 Years Treatment Between Degarelix and Goserelin
PFS failure is defined as either PSA failure, introduction of additional therapy related to prostate cancer (radiation, anti-androgens or second-line treatment), or death, whichever is first. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no PFS failure.
Time frame: From baseline to 3 years
Population: CS35 (NCT00946920)/CS35A Full Analysis Set (degarelix n=565; goserelin n=282). The analysis population was pre-specified in the study protocol and statistical analysis plan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 240 mg/480 mg | Hazard Ratio of PFS Failure Rates During 3 Years Treatment Between Degarelix and Goserelin | 71.5 percentage of no PFS failure |
| Goserelin Acetate | Hazard Ratio of PFS Failure Rates During 3 Years Treatment Between Degarelix and Goserelin | 69.0 percentage of no PFS failure |
Comparison: The hazard ratio was estimated using the Cox proportional hazard model.p-value: 0.124495% CI: [0.574, 1.07]Cox proportional hazard model
Secondary
Hazard Ratio of PSA Failure Rates During 3 Years Treatment Between Degarelix and Goserelin
PSA failure is defined as increase in serum PSA of 50%, and at least 5 ng/mL, compared to nadir, measured on two consecutive occasions at least 2 weeks apart. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no PSA failure.
Time frame: From baseline to 3 years
Population: CS35 (NCT00946920)/CS35A Full Analysis Set (degarelix n=565; goserelin n=282). The analysis population was pre-specified in the study protocol and statistical analysis plan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 240 mg/480 mg | Hazard Ratio of PSA Failure Rates During 3 Years Treatment Between Degarelix and Goserelin | 77.5 percentage of no PSA failure |
| Goserelin Acetate | Hazard Ratio of PSA Failure Rates During 3 Years Treatment Between Degarelix and Goserelin | 79.6 percentage of no PSA failure |
Comparison: The hazard ratio was estimated using the Cox proportional hazard model.95% CI: [0.58, 1.263]
Secondary
Hazard Ratio of Testosterone Escape Rates During 3 Years' Treatment Between Degarelix and Goserelin
Testosterone escape is defined as serum levels \>0.5 ng/mL. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no testosterone escape.
Time frame: From baseline to 3 years
Population: CS35 (NCT00946920)/CS35A Full Analysis Set (degarelix n=565; goserelin n=282). The analysis population was pre-specified in the study protocol and statistical analysis plan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 240 mg/480 mg | Hazard Ratio of Testosterone Escape Rates During 3 Years' Treatment Between Degarelix and Goserelin | 83.7 percentage of no testosterone escape |
| Goserelin Acetate | Hazard Ratio of Testosterone Escape Rates During 3 Years' Treatment Between Degarelix and Goserelin | 96.7 percentage of no testosterone escape |
Comparison: The hazard ratio was estimated using the Cox proportional hazard model.p-value: 0.000595% CI: [1.739, 7.09]Cox proportional hazard model
Secondary
Hazard Ratio of the Rates of Introduction of Additional Therapy Related to Prostate Cancer During 3 Years' Treatment Between Degarelix and Goserelin
Additional therapy related to prostate cancer included radiation, anti-androgens and second-line treatment. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no additional therapy related to prostate cancer.
Time frame: From baseline to 3 years
Population: CS35 (NCT00946920)/CS35A Full Analysis Set (degarelix n=565; goserelin n=282). The analysis population was pre-specified in the study protocol and statistical analysis plan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 240 mg/480 mg | Hazard Ratio of the Rates of Introduction of Additional Therapy Related to Prostate Cancer During 3 Years' Treatment Between Degarelix and Goserelin | 84.5 percentage of no additional therapy |
| Goserelin Acetate | Hazard Ratio of the Rates of Introduction of Additional Therapy Related to Prostate Cancer During 3 Years' Treatment Between Degarelix and Goserelin | 83.4 percentage of no additional therapy |
Comparison: The hazard ratio was estimated using the Cox proportional hazard model.p-value: 0.14395% CI: [0.493, 1.108]Cox proportional hazard model
Secondary
Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin
Median PSA levels are presented as absolute values in nanograms per milliliter (ng/mL) at baseline and after 1, 6, 12, 19, and 22 months. One month equals 28 days. After 22 months, only a limited number of samples were analysed.
Time frame: Baseline and after 1, 6, 12, 19, and 22 months
Population: CS35 (NCT00946920)/CS35A Full Analysis Set (degarelix n=565; goserelin n=282). The analysis population was pre-specified in the study protocol and statistical analysis plan.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Degarelix 240 mg/480 mg | Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin | Baseline | 19 ng/mL |
| Degarelix 240 mg/480 mg | Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin | Month 1 | 3.79 ng/mL |
| Degarelix 240 mg/480 mg | Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin | Month 6 | 0.82 ng/mL |
| Degarelix 240 mg/480 mg | Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin | Month 12 | 0.6 ng/mL |
| Degarelix 240 mg/480 mg | Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin | Month 19 | 0.54 ng/mL |
| Degarelix 240 mg/480 mg | Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin | Month 22 | 0.535 ng/mL |
| Goserelin Acetate | Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin | Month 19 | 0.28 ng/mL |
| Goserelin Acetate | Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin | Baseline | 19.1 ng/mL |
| Goserelin Acetate | Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin | Month 12 | 0.43 ng/mL |
| Goserelin Acetate | Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin | Month 1 | 6.5 ng/mL |
| Goserelin Acetate | Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin | Month 22 | 0.26 ng/mL |
| Goserelin Acetate | Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin | Month 6 | 0.73 ng/mL |
Secondary
Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin
Median testosterone levels are presented as absolute values in nanograms per milliliter (ng/mL) at baseline and after 1, 6, 12, 19, and 22 months. One month equals 28 days. After 22 months, only a limited number of samples were analysed.
Time frame: Baseline and after 1, 6, 12, 19, and 22 months
Population: CS35 (NCT00946920)/CS35A Full Analysis Set (degarelix n=565; goserelin n=282). The analysis population was pre-specified in the study protocol and statistical analysis plan.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Degarelix 240 mg/480 mg | Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin | Baseline | 4.52 ng/mL |
| Degarelix 240 mg/480 mg | Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin | Month 1 | 0.10 ng/mL |
| Degarelix 240 mg/480 mg | Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin | Month 6 | 0.09 ng/mL |
| Degarelix 240 mg/480 mg | Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin | Month 12 | 0.10 ng/mL |
| Degarelix 240 mg/480 mg | Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin | Month 19 | 0.11 ng/mL |
| Degarelix 240 mg/480 mg | Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin | Month 22 | 0.11 ng/mL |
| Goserelin Acetate | Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin | Month 19 | 0.05 ng/mL |
| Goserelin Acetate | Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin | Baseline | 4.62 ng/mL |
| Goserelin Acetate | Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin | Month 12 | 0.09 ng/mL |
| Goserelin Acetate | Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin | Month 1 | 0.16 ng/mL |
| Goserelin Acetate | Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin | Month 22 | 0.05 ng/mL |
| Goserelin Acetate | Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin | Month 6 | 0.09 ng/mL |