Castrate-resistant Prostate Cancer
Conditions
Brief summary
This is a multi-national, multi-center, open-label, single-arm extension study for the prolongation of bone metastasis-free survival in men with hormone-refractory (androgen independent) prostate cancer. Patients currently participating in the phase 3 study 20050147 (NCT00286091) will be offered this study if a positive benefit:risk compared with placebo is determined in the 20050147 study. The primary endpoint of the 20050147 study is bone metastases-free survival determined by the time to first occurrence of bone metastases (either symptomatic or asymptomatic) or death from any cause. Participants will receive open-label denosumab administered once every 4 weeks (Q4W) subcutaneously (SC) until they developed a bone metastasis or for up to 3 years, whichever comes first.
Interventions
BIOLOGICALDenosumab
Administered by subcutaneous injection
Sponsors
Amgen
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
* Subjects currently undergoing every 4 weeks scheduled assessments in the phase 3 study 20050147 * Subjects must sign the informed consent before any study specific procedures are performed
Exclusion criteria
* Developed sensitivity to mammalian cell derived drug products during the 20050147 study * Currently receiving any unapproved investigational product other than denosumab * Any disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or comply with study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | From the first dose of open-label denosumab until 4 weeks after the last; maximum time on study was 37 months. Follow-up survival information was collected for up to 3 years after the last dose of blinded investigation product in the 20050147 study. | A serious adverse event is defined as an adverse event that meets at least one of the following serious criteria: • fatal, • life threatening, • requires in-patient hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, • congenital anomaly/birth defect, and/or • other significant medical hazard. The adverse event severity grading scale used was the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, according to the following: Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE. The investigator assessed whether each adverse event was possibly related to the investigational product (IP). |
| Percent Change From Baseline in Laboratory Values | Baseline and Week 49 | — |
| Number of Participants With Anti-denosumab Neutralizing Antibody Formation | 3 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | Baseline and Week 49 | A scale used to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work); 2 = Ambulatory and capable of all self care, but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry out any self-care. Totally confined to bed or chair; 5 = Dead. |
Countries
Czechia, United Kingdom
Participant flow
Recruitment details
This was a single-arm, open-label extension (OLE) phase of a phase 3, randomized, double-blind study (Study 20050147; NCT00286091) comparing denosumab with placebo on prolonging bone metastasis-free survival in men with hormone-refractory (androgen independent) prostate cancer.
Pre-assignment details
All participants received denosumab during the OLE phase; in the parent study participants were initially randomized in a blinded manner to receive denosumab at a dose of 120 mg or placebo every 4 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Denosumab Participants who received placebo in the parent study received open-label denosumab 120 mg by subcutaneous injecton once every 4 weeks (Q4W) for up to 3 years. | 11 |
| Denosumab/Denosumab Participants who received denosumab in the parent study received open-label denosumab 120 mg by subcutaneous injecton once every 4 weeks (Q4W) for up to 3 years. | 7 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Disease Progression | 1 | 1 |
| Overall Study | Physician Decision | 5 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Placebo/Denosumab | Total | Denosumab/Denosumab |
|---|---|---|---|
| Age, Continuous | 71.6 years STANDARD_DEVIATION 4.3 | 71.1 years STANDARD_DEVIATION 5.6 | 70.3 years STANDARD_DEVIATION 7.4 |
| Albumin-adjusted calcium | 2.44 mmol/L STANDARD_DEVIATION 0.1 | 2.43 mmol/L STANDARD_DEVIATION 0.08 | 2.42 mmol/L STANDARD_DEVIATION 0.04 |
| Creatinine | 88.40 umol/L STANDARD_DEVIATION 14.25 | 88.89 umol/L STANDARD_DEVIATION 17.8 | 89.66 umol/L STANDARD_DEVIATION 23.63 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0 | 7 participants | 12 participants | 5 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1 | 4 participants | 5 participants | 1 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 2 | 0 participants | 1 participants | 1 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 3 | 0 participants | 0 participants | 0 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 4 | 0 participants | 0 participants | 0 participants |
| Phosphorus | 1.09 mmol/L STANDARD_DEVIATION 0.22 | 1.06 mmol/L STANDARD_DEVIATION 0.22 | 1.01 mmol/L STANDARD_DEVIATION 0.24 |
| Race/Ethnicity, Customized White or Caucasian | 11 participants | 18 participants | 7 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 11 Participants | 18 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 11 | 6 / 7 |
| serious Total, serious adverse events | 7 / 11 | 4 / 7 |
Outcome results
Primary
Number of Participants With Anti-denosumab Neutralizing Antibody Formation
Time frame: 3 years
Population: Participants exposed to open-label denosumab with ≥ 1 antibody sample
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Denosumab | Number of Participants With Anti-denosumab Neutralizing Antibody Formation | 0 participants |
| Denosumab/Denosumab | Number of Participants With Anti-denosumab Neutralizing Antibody Formation | 0 participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths
A serious adverse event is defined as an adverse event that meets at least one of the following serious criteria: • fatal, • life threatening, • requires in-patient hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, • congenital anomaly/birth defect, and/or • other significant medical hazard. The adverse event severity grading scale used was the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, according to the following: Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE. The investigator assessed whether each adverse event was possibly related to the investigational product (IP).
Time frame: From the first dose of open-label denosumab until 4 weeks after the last; maximum time on study was 37 months. Follow-up survival information was collected for up to 3 years after the last dose of blinded investigation product in the 20050147 study.
Population: Safety analysis set, which included participants who had properly documented informed consent for protocol 20080585 and received at least 1 dose of open-label denosumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | AE leading to IP discontinuation | 4 participants |
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Fatal AE related to IP | 0 participants |
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Serious adverse event | 7 participants |
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | AE related to IP leading to study discontinuation | 1 participants |
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | CTCAE Grade 3, 4, or 5 | 6 participants |
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | AE related to IP leading to IP discontinuation | 1 participants |
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | AE leading to study discontinuation | 2 participants |
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | AE related to IP and CTCAE Grade 3, 4, or 5 | 0 participants |
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | AE related to investigational product (IP) | 2 participants |
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Deaths | 4 participants |
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Fatal adverse event | 2 participants |
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Deaths on study | 2 participants |
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Serious AE related to IP | 0 participants |
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Deaths during the safety follow-up | 2 participants |
| Placebo/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Any adverse event (AE) | 11 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Deaths during the safety follow-up | 1 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Any adverse event (AE) | 7 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Serious adverse event | 4 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Fatal adverse event | 0 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | AE leading to study discontinuation | 1 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | AE leading to IP discontinuation | 1 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | CTCAE Grade 3, 4, or 5 | 2 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | AE related to investigational product (IP) | 3 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Serious AE related to IP | 2 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Fatal AE related to IP | 0 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | AE related to IP leading to study discontinuation | 1 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | AE related to IP leading to IP discontinuation | 1 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | AE related to IP and CTCAE Grade 3, 4, or 5 | 1 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Deaths | 1 participants |
| Denosumab/Denosumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | Deaths on study | 0 participants |
Primary
Percent Change From Baseline in Laboratory Values
Time frame: Baseline and Week 49
Population: Safety analysis set with available laboratory data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Denosumab | Percent Change From Baseline in Laboratory Values | Albumin-adjusted Calcium | -0.9 percent change | Standard Deviation 2.5 |
| Placebo/Denosumab | Percent Change From Baseline in Laboratory Values | Alkaline Phosphatase | -23.8 percent change | Standard Deviation 21.8 |
| Placebo/Denosumab | Percent Change From Baseline in Laboratory Values | Creatinine | 16.3 percent change | Standard Deviation 31.5 |
| Placebo/Denosumab | Percent Change From Baseline in Laboratory Values | Phosphorus | -2.6 percent change | Standard Deviation 25.2 |
| Denosumab/Denosumab | Percent Change From Baseline in Laboratory Values | Phosphorus | 0.0 percent change | Standard Deviation 10.4 |
| Denosumab/Denosumab | Percent Change From Baseline in Laboratory Values | Albumin-adjusted Calcium | 1.1 percent change | Standard Deviation 3.1 |
| Denosumab/Denosumab | Percent Change From Baseline in Laboratory Values | Creatinine | 2.4 percent change | Standard Deviation 5.8 |
| Denosumab/Denosumab | Percent Change From Baseline in Laboratory Values | Alkaline Phosphatase | -1.6 percent change | Standard Deviation 20.5 |
Secondary
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
A scale used to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work); 2 = Ambulatory and capable of all self care, but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry out any self-care. Totally confined to bed or chair; 5 = Dead.
Time frame: Baseline and Week 49
Population: Safety analysis set with available data at both time points
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo/Denosumab | Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | 2-point increase in PS | 0 participants |
| Placebo/Denosumab | Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | No change | 10 participants |
| Placebo/Denosumab | Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | 3-point increase in PS | 0 participants |
| Placebo/Denosumab | Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | 1-point decrease in PS | 0 participants |
| Placebo/Denosumab | Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | 1-point increase in PS | 0 participants |
| Placebo/Denosumab | Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | 2-point decrease in PS | 0 participants |
| Placebo/Denosumab | Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | 4-point increase in PS | 0 participants |
| Denosumab/Denosumab | Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | 2-point decrease in PS | 0 participants |
| Denosumab/Denosumab | Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | 4-point increase in PS | 0 participants |
| Denosumab/Denosumab | Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | 3-point increase in PS | 0 participants |
| Denosumab/Denosumab | Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | 2-point increase in PS | 0 participants |
| Denosumab/Denosumab | Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | 1-point increase in PS | 1 participants |
| Denosumab/Denosumab | Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | No change | 5 participants |
| Denosumab/Denosumab | Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | 1-point decrease in PS | 0 participants |