Trial Outcomes & Findings for Denosumab for Prolonging Bone Metastasis-Free Survival in Men With Hormone-Refractory Prostate Cancer (NCT NCT01824342)

Last Updated: 2015-03-05

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

18 participants

Primary outcome timeframe

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.

Results posted on

2015-03-05

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	11	7
Overall Study COMPLETED	2	2
Overall Study NOT COMPLETED	9	5

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Withdrawal by Subject	0	3
Overall Study Adverse Event	1	1
Overall Study Disease Progression	1	1
Overall Study Physician Decision	5	0
Overall Study Death	2	0

Baseline Characteristics

Denosumab for Prolonging Bone Metastasis-Free Survival in Men With Hormone-Refractory Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/Denosumab n=11 Participants 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.	Denosumab/Denosumab n=7 Participants 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.	Total n=18 Participants Total of all reporting groups
Age, Continuous	71.6 years STANDARD_DEVIATION 4.3 • n=5 Participants	70.3 years STANDARD_DEVIATION 7.4 • n=7 Participants	71.1 years STANDARD_DEVIATION 5.6 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
Race/Ethnicity, Customized White or Caucasian	11 participants n=5 Participants	7 participants n=7 Participants	18 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0	7 participants n=5 Participants	5 participants n=7 Participants	12 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 2	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 3	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 4	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Albumin-adjusted calcium	2.44 mmol/L STANDARD_DEVIATION 0.10 • n=5 Participants	2.42 mmol/L STANDARD_DEVIATION 0.04 • n=7 Participants	2.43 mmol/L STANDARD_DEVIATION 0.08 • n=5 Participants
Creatinine	88.40 umol/L STANDARD_DEVIATION 14.25 • n=5 Participants	89.66 umol/L STANDARD_DEVIATION 23.63 • n=7 Participants	88.89 umol/L STANDARD_DEVIATION 17.80 • n=5 Participants
Phosphorus	1.09 mmol/L STANDARD_DEVIATION 0.22 • n=5 Participants	1.01 mmol/L STANDARD_DEVIATION 0.24 • n=7 Participants	1.06 mmol/L STANDARD_DEVIATION 0.22 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo/Denosumab n=11 Participants 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.	Denosumab/Denosumab n=7 Participants 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.
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths Any adverse event (AE)	11 participants	7 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths Serious adverse event	7 participants	4 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths Fatal adverse event	2 participants	0 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths AE leading to study discontinuation	2 participants	1 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths AE leading to IP discontinuation	4 participants	1 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths CTCAE Grade 3, 4, or 5	6 participants	2 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths AE related to investigational product (IP)	2 participants	3 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths Serious AE related to IP	0 participants	2 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths Fatal AE related to IP	0 participants	0 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths AE related to IP leading to study discontinuation	1 participants	1 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths AE related to IP leading to IP discontinuation	1 participants	1 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths AE related to IP and CTCAE Grade 3, 4, or 5	0 participants	1 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths Deaths	4 participants	1 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths Deaths on study	2 participants	0 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths Deaths during the safety follow-up	2 participants	1 participants

PRIMARY outcome

Timeframe: Baseline and Week 49

Population: Safety analysis set with available laboratory data at each time point.

Outcome measures

Outcome measures
Measure	Placebo/Denosumab n=10 Participants 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.	Denosumab/Denosumab n=6 Participants 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.
Percent Change From Baseline in Laboratory Values Albumin-adjusted Calcium	-0.9 percent change Standard Deviation 2.5	1.1 percent change Standard Deviation 3.1
Percent Change From Baseline in Laboratory Values Alkaline Phosphatase	-23.8 percent change Standard Deviation 21.8	-1.6 percent change Standard Deviation 20.5
Percent Change From Baseline in Laboratory Values Creatinine	16.3 percent change Standard Deviation 31.5	2.4 percent change Standard Deviation 5.8
Percent Change From Baseline in Laboratory Values Phosphorus	-2.6 percent change Standard Deviation 25.2	0.0 percent change Standard Deviation 10.4

PRIMARY outcome

Timeframe: 3 years

Population: Participants exposed to open-label denosumab with ≥ 1 antibody sample

Outcome measures

Outcome measures
Measure	Placebo/Denosumab n=10 Participants 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.	Denosumab/Denosumab n=7 Participants 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.
Number of Participants With Anti-denosumab Neutralizing Antibody Formation	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline and Week 49

Population: Safety analysis set with available data at both time points

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.

Outcome measures

Outcome measures
Measure	Placebo/Denosumab n=10 Participants 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.	Denosumab/Denosumab n=6 Participants 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.
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 4-point increase in PS	0 participants	0 participants
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 3-point increase in PS	0 participants	0 participants
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 2-point increase in PS	0 participants	0 participants
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 1-point increase in PS	0 participants	1 participants
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) No change	10 participants	5 participants
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 1-point decrease in PS	0 participants	0 participants
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 2-point decrease in PS	0 participants	0 participants

Adverse Events

Placebo/ Denosumab 120 mg Q4W

Serious events: 7 serious events

Other events: 11 other events

Deaths: 0 deaths

Denosumab/ Denosumab 120 mg Q4W

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo/ Denosumab 120 mg Q4W n=11 participants at risk 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.	Denosumab/ Denosumab 120 mg Q4W n=7 participants at risk 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.
Cardiac disorders Mitral valve incompetence	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Myocardial infarction	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Congenital, familial and genetic disorders Phimosis	0.00% 0/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	14.3% 1/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Constipation	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Death	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Medical device complication	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Cystitis	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Lower respiratory tract infection	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Urinary tract infection	18.2% 2/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Haemoglobin decreased	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Urinary sediment present	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Muscular weakness	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.00% 0/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	28.6% 2/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Pain in extremity	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchial carcinoma	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant anorectal neoplasm	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	18.2% 2/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Hypoaesthesia	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Bladder neck obstruction	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Calculus bladder	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Dysuria	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Haematuria	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Hydronephrosis	18.2% 2/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Nocturia	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Renal impairment	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Urethral haemorrhage	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Urethral stenosis	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Urinary incontinence	9.1% 1/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Urinary retention	18.2% 2/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	14.3% 1/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/11 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	14.3% 1/7 • 3 years Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.