Prostate Cancer
Conditions
Keywords
Hormone refractory prostate cancer, Agonist treatment failure
Brief summary
This was an open-label, multi-centre, uncontrolled, exploratory trial with a duration of 12 months in two cohorts. The trial aimed to investigate Degarelix as a second-line hormonal treatment in Prostate Cancer patients who experienced PSA-Failure following gonadotropin-releasing hormone (GnRH) agonist treatment. The two cohorts differ in Testosterone levels at inclusion.
Interventions
DRUGdegarelix
Starting dose of 240 mg (40 mg/mL). Maintenance doses of 80 mg (20 mg/mL).
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has given written informed consent before any trial-related activity is performed. * Patient is 18 years or older. * Histologically confirmed prostate cancer. * Patient has received GnRH receptor agonist therapy for a duration of at least 12 months (the first dose of GnRH-antagonist is to be administered when the next dose of the GnRH-agonist would have been due). * Patient has experienced rising PSA levels although receiving GnRH agonist therapy, defined as two consecutive rises of PSA at least two weeks apart in two 50% increases over the nadir, and at least one PSA value of \>2.5 ng/mL within the last six months. * Testosterone on castrate level (defined as ≤ 0.5 ng/mL) (cohort 1); Testosterone ≥0.2 ng/mL at inclusion (cohort 2) * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. * Estimated life expectancy at least 12 months.
Exclusion criteria
* 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. * Ongoing GnRH agonist therapy (last dose of previous GnRH agonist must have been received before Visit 1). * Any pre-trial secondary hormonal manipulation (including antiandrogens) after PSA increase as described as above and before trial entry. Antiandrogens as part of complete androgen blockade must have been discontinued at least three months before first dose of trial medication. * Previous or current treatment with chemotherapy (e.g. estramustine) for prostate cancer. * Known hypersensitivity towards any component of the investigational medical product. * History of severe uncontrolled asthma, anaphylactic reactions, or severe urticaria and/or angioedema. * Known or suspected clinically significant liver and/or biliary disease. * Any clinically significant laboratory abnormalities, disorders, or other condition, including alcohol or drug abuse, which may affect the patient's health or the outcome of the trial as judged by the Investigator. * Patient has a clinically significant disorder (other than prostate cancer) including, but not limited to, renal, hematological, 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. * Patient has a mental incapacity or language barriers precluding adequate understanding or co-operation. * Patient has received an investigational drug within the last 28 days preceding screening visit. Or longer if considered to possibly influencing the outcome of the current trial. * Previous participation in any degarelix trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants' Response in Prostate-Specific Antigen (PSA) Level at Three Months As Compared to Baseline | Day 0 (baseline), 3 months | Response to treatment was defined as: * Response (stabilisation or decrease): Difference ≤ +10% of Baseline level * No response (increase): Difference \> +10% of Baseline level |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants' Response in Prostate-Specific Antigen (PSA) Level at Two Months As Compared to Baseline | Day 0 (baseline), 2 months | Response to treatment was defined as: * Response (stabilisation or decrease): Difference ≤ +10% of Baseline level * No response (increase): Difference \> +10% of Baseline level. Per protocol, the two month timeframe was only analyzed for cohort 2. |
| Participants at Testosterone Castrate Level Throughout the Study | up to month 12 | Participants who had no post-baseline serum testosterone level above castrate level which was \<=0.5 ng/mL. |
| Change From Baseline in Serum Levels of Testosterone at the Last Visit | Day 0 (baseline), up to month 12 (last visit) | — |
| Change From Baseline in Serum Levels of Prostate-Specific Antigen (PSA) at Last Visit | Day 0 (baseline), up to month 12 (last visit) | — |
| Percent Change From Baseline in Serum Levels of Luteinising Hormone (LH) at the Last Visit | Day 0 (baseline), up to month 12 (last visit) | LH is measured in IU/L |
| Participants' Response in Prostate-Specific Antigen (PSA) Level at One Month As Compared to Baseline | Day 0 (baseline), 1 month | Response to treatment was defined as: * Response (stabilisation or decrease): Difference ≤ +10% of Baseline level * No response (increase): Difference \> +10% of Baseline level. Per protocol, the one month timeframe was only analyzed for cohort 2. |
| Participants at Testosterone Level <=0.2 ng/mL Throughout the Study | up to month 12 | Participants in Cohort 2 who had no post-baseline serum testosterone level above 0.2 ng/mL. |
| Participants at Testosterone Level <=0.32 ng/mL Throughout the Study | up to month 12 | Participants in Cohort 2 who had no post-baseline serum testosterone level above 0.32 ng/mL |
| Participants With Prostate-Specific Antigen (PSA) Progression Throughout the Study | up to month 12 | Counts of participants who had PSA progression during the study. PSA progression was defined as PSA \>+10% of baseline value. |
| Kaplan-Meier Estimate for Overall Survival | up to month 12 | The overall survival time was defined as number of days from first treatment dose to date of death. If a patient did not die then the patient's data were censored at the date of last visit. |
| Change From Baseline in Serum Levels of Follicle-Stimulating Hormone (FSH) at the Last Visit | Day 0 (baseline), up to month 12 (last visit) | — |
Countries
Germany
Participant flow
Recruitment details
Cohort 1 comprised a broad spectrum of biochemically relapsed participants (on castrate level) on long term hormonal treatment in different stages of the disease (primarily advance stages), however not in need of chemotherapy. The second cohort was similar, although testosterone levels were to be above castrate level (≥0.32 ng/mL).
Participants by arm
| Arm | Count |
|---|---|
| Degarelix - Cohort 1 Participants with baseline testosterone at castrate level. Starting dose: 240 mg by subcutaneous (s.c.) injection in the abdomen on Day 0. Maintenance dose: a maximum of 11 doses of 80 mg degarelix were given 28 days apart via single s.c. injections. | 24 |
| Degarelix - Cohort 2 Participants with baseline testosterone above castrate level (≥0.32 ng/mL ). Starting dose: 240 mg by subcutaneous (s.c.) injection in the abdomen on Day 0. Maintenance dose: a maximum of 11 doses of 80 mg degarelix were given 28 days apart via single s.c. injections. | 12 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lack of Efficacy | 19 | 8 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Total | Degarelix - Cohort 2 | Degarelix - Cohort 1 |
|---|---|---|---|
| Age Continuous | 73.9 years STANDARD_DEVIATION 8.08 | 76.5 years STANDARD_DEVIATION 4.68 | 72.7 years STANDARD_DEVIATION 9.11 |
| Eastern Cooporative Oncology Group (ECOG) Performance Status Ambulatory, unable to work | 8 participants | 1 participants | 7 participants |
| Eastern Cooporative Oncology Group (ECOG) Performance Status Capable of only limited selfcare | 0 participants | 0 participants | 0 participants |
| Eastern Cooporative Oncology Group (ECOG) Performance Status Completely disabled | 0 participants | 0 participants | 0 participants |
| Eastern Cooporative Oncology Group (ECOG) Performance Status Fully active | 0 participants | 0 participants | 0 participants |
| Eastern Cooporative Oncology Group (ECOG) Performance Status Restricted, but ambulatory | 28 participants | 11 participants | 17 participants |
| Gleason Score 2-4 | 4 participants | 3 participants | 1 participants |
| Gleason Score 5-6 | 6 participants | 2 participants | 4 participants |
| Gleason Score 7-10 | 26 participants | 7 participants | 19 participants |
| Height | 1.73 meters STANDARD_DEVIATION 0.06 | 1.72 meters STANDARD_DEVIATION 0.05 | 1.74 meters STANDARD_DEVIATION 0.06 |
| Race/Ethnicity, Customized HIspanic or Latino | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 36 participants | 12 participants | 24 participants |
| Race/Ethnicity, Customized Other | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White | 36 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 36 Participants | 12 Participants | 24 Participants |
| Stage of Prostate Cancer at Diagnosis Localized | 8 participants | 4 participants | 4 participants |
| Stage of Prostate Cancer at Diagnosis Locally advanced | 12 participants | 1 participants | 11 participants |
| Stage of Prostate Cancer at Diagnosis Metastatic | 8 participants | 2 participants | 6 participants |
| Stage of Prostate Cancer at Diagnosis Not classifiable | 8 participants | 5 participants | 3 participants |
| Stage of Prostate Cancer at Enrolment Localized | 3 participants | 2 participants | 1 participants |
| Stage of Prostate Cancer at Enrolment Locally advanced | 9 participants | 0 participants | 9 participants |
| Stage of Prostate Cancer at Enrolment Metastatic | 12 participants | 5 participants | 7 participants |
| Stage of Prostate Cancer at Enrolment Not classifiable | 12 participants | 5 participants | 7 participants |
| Weight | 89.6 kg STANDARD_DEVIATION 15.5 | 87.6 kg STANDARD_DEVIATION 11 | 90.5 kg STANDARD_DEVIATION 17.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 25 | 10 / 12 |
| serious Total, serious adverse events | 3 / 25 | 1 / 12 |
Outcome results
Primary
Participants' Response in Prostate-Specific Antigen (PSA) Level at Three Months As Compared to Baseline
Response to treatment was defined as: * Response (stabilisation or decrease): Difference ≤ +10% of Baseline level * No response (increase): Difference \> +10% of Baseline level
Time frame: Day 0 (baseline), 3 months
Population: Intent to treat population. Last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Degarelix - Cohort 1 | Participants' Response in Prostate-Specific Antigen (PSA) Level at Three Months As Compared to Baseline | Response | 16.67 percentage of participants |
| Degarelix - Cohort 1 | Participants' Response in Prostate-Specific Antigen (PSA) Level at Three Months As Compared to Baseline | No Response | 83.33 percentage of participants |
| Degarelix - Cohort 2 | Participants' Response in Prostate-Specific Antigen (PSA) Level at Three Months As Compared to Baseline | Response | 33.33 percentage of participants |
| Degarelix - Cohort 2 | Participants' Response in Prostate-Specific Antigen (PSA) Level at Three Months As Compared to Baseline | No Response | 66.67 percentage of participants |
Secondary
Change From Baseline in Serum Levels of Follicle-Stimulating Hormone (FSH) at the Last Visit
Time frame: Day 0 (baseline), up to month 12 (last visit)
Population: Intent to treat population with a baseline and at least one scheduled post-baseline measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Degarelix - Cohort 1 | Change From Baseline in Serum Levels of Follicle-Stimulating Hormone (FSH) at the Last Visit | -1.64 IU/L | Standard Deviation 3.01 |
| Degarelix - Cohort 2 | Change From Baseline in Serum Levels of Follicle-Stimulating Hormone (FSH) at the Last Visit | -2.01 IU/L | Standard Deviation 1.72 |
Secondary
Change From Baseline in Serum Levels of Prostate-Specific Antigen (PSA) at Last Visit
Time frame: Day 0 (baseline), up to month 12 (last visit)
Population: Intent to treat population with a baseline and at least one scheduled post-baseline measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Degarelix - Cohort 1 | Change From Baseline in Serum Levels of Prostate-Specific Antigen (PSA) at Last Visit | 18 ng/mL | Standard Deviation 29 |
| Degarelix - Cohort 2 | Change From Baseline in Serum Levels of Prostate-Specific Antigen (PSA) at Last Visit | 54 ng/mL | Standard Deviation 116 |
Secondary
Change From Baseline in Serum Levels of Testosterone at the Last Visit
Time frame: Day 0 (baseline), up to month 12 (last visit)
Population: Intent to treat population with a baseline and at least one scheduled post-baseline measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Degarelix - Cohort 1 | Change From Baseline in Serum Levels of Testosterone at the Last Visit | -0.039 ng/mL | Standard Deviation 0.175 |
| Degarelix - Cohort 2 | Change From Baseline in Serum Levels of Testosterone at the Last Visit | -0.038 ng/mL | Standard Deviation 0.631 |
Secondary
Kaplan-Meier Estimate for Overall Survival
The overall survival time was defined as number of days from first treatment dose to date of death. If a patient did not die then the patient's data were censored at the date of last visit.
Time frame: up to month 12
Population: Intent to treat population.~Analysis was not performed since no participants died during study.
Secondary
Participants at Testosterone Castrate Level Throughout the Study
Participants who had no post-baseline serum testosterone level above castrate level which was \<=0.5 ng/mL.
Time frame: up to month 12
Population: Intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix - Cohort 1 | Participants at Testosterone Castrate Level Throughout the Study | 24 participants |
| Degarelix - Cohort 2 | Participants at Testosterone Castrate Level Throughout the Study | 11 participants |
Secondary
Participants at Testosterone Level <=0.2 ng/mL Throughout the Study
Participants in Cohort 2 who had no post-baseline serum testosterone level above 0.2 ng/mL.
Time frame: up to month 12
Population: Full analysis set. Per the protocol, this analysis was only performed on Cohort 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix - Cohort 2 | Participants at Testosterone Level <=0.2 ng/mL Throughout the Study | 8 participants |
Secondary
Participants at Testosterone Level <=0.32 ng/mL Throughout the Study
Participants in Cohort 2 who had no post-baseline serum testosterone level above 0.32 ng/mL
Time frame: up to month 12
Population: Full analysis set. Per the protocol, this analysis was only performed on Cohort 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix - Cohort 2 | Participants at Testosterone Level <=0.32 ng/mL Throughout the Study | 9 participants |
Secondary
Participants' Response in Prostate-Specific Antigen (PSA) Level at One Month As Compared to Baseline
Response to treatment was defined as: * Response (stabilisation or decrease): Difference ≤ +10% of Baseline level * No response (increase): Difference \> +10% of Baseline level. Per protocol, the one month timeframe was only analyzed for cohort 2.
Time frame: Day 0 (baseline), 1 month
Population: Full analysis set of participants with baseline and month 1 values. Per protocol, the one month timeframe was only analyzed for cohort 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Degarelix - Cohort 2 | Participants' Response in Prostate-Specific Antigen (PSA) Level at One Month As Compared to Baseline | Response | 66.67 percentage of participants |
| Degarelix - Cohort 2 | Participants' Response in Prostate-Specific Antigen (PSA) Level at One Month As Compared to Baseline | No Response | 33.33 percentage of participants |
Secondary
Participants' Response in Prostate-Specific Antigen (PSA) Level at Two Months As Compared to Baseline
Response to treatment was defined as: * Response (stabilisation or decrease): Difference ≤ +10% of Baseline level * No response (increase): Difference \> +10% of Baseline level. Per protocol, the two month timeframe was only analyzed for cohort 2.
Time frame: Day 0 (baseline), 2 months
Population: Full analysis set of participants with baseline and month 2 values. Per protocol, the two month timeframe was only analyzed for cohort 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Degarelix - Cohort 2 | Participants' Response in Prostate-Specific Antigen (PSA) Level at Two Months As Compared to Baseline | Response | 40.00 percentage of participants |
| Degarelix - Cohort 2 | Participants' Response in Prostate-Specific Antigen (PSA) Level at Two Months As Compared to Baseline | No Response | 60.00 percentage of participants |
Secondary
Participants With Prostate-Specific Antigen (PSA) Progression Throughout the Study
Counts of participants who had PSA progression during the study. PSA progression was defined as PSA \>+10% of baseline value.
Time frame: up to month 12
Population: Intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix - Cohort 1 | Participants With Prostate-Specific Antigen (PSA) Progression Throughout the Study | 21 participants |
| Degarelix - Cohort 2 | Participants With Prostate-Specific Antigen (PSA) Progression Throughout the Study | 11 participants |
Secondary
Percent Change From Baseline in Serum Levels of Luteinising Hormone (LH) at the Last Visit
LH is measured in IU/L
Time frame: Day 0 (baseline), up to month 12 (last visit)
Population: Intent to treat population with a baseline and at least one scheduled post-baseline measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Degarelix - Cohort 1 | Percent Change From Baseline in Serum Levels of Luteinising Hormone (LH) at the Last Visit | 58 percentage of baseline | Standard Deviation 286 |
| Degarelix - Cohort 2 | Percent Change From Baseline in Serum Levels of Luteinising Hormone (LH) at the Last Visit | 123 percentage of baseline | Standard Deviation 277 |