Trial Outcomes & Findings for Effect of Denosumab on Cellular Biomarkers in the Human Breast (NCT NCT02099461)
NCT ID: NCT02099461
Last Updated: 2015-09-24
Results Overview
Ki-67 is a marker for cell proliferation. Participants underwent percutaneous core needle breast biopsies on Day 1 (Baseline, prior to treatment) and Day 28. Levels of Ki67 were measured using immunohistochemical staining and digital imaging. The proliferation index was calculated as the percentage of Ki-67 positive terminal ductal lobular unit (TDLU) and duct epithelial cells. The higher the percentage, the higher the rate of epithelial cell proliferation.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
82 participants
Primary outcome timeframe
Baseline and Day 28
Results posted on
2015-09-24
Participant Flow
On study day 1, eligible participants were randomized into 1 of 3 treatment assignments. Randomization was stratified by average length of menstrual cycle (\< 28 days, equal to 28 days, and \> 28 days).
Participant milestones
| Measure |
No Treatment
Participants received no treatment and underwent percutaneous core needle breast biopsies on Day 1 and Day 28.
|
Denosumab 60 mg
Participants received 60 mg denosumab by subcutaneous injection on Day 1 and underwent percutaneous core needle breast biopsies on Day 1 and Day 28.
|
Denosumab 120 mg
Participants received 120 mg denosumab by subcutaneous injection on Day 1 and underwent percutaneous core needle breast biopsies on Day 1 and Day 28.
|
|---|---|---|---|
|
Overall Study
STARTED
|
27
|
27
|
28
|
|
Overall Study
COMPLETED
|
27
|
27
|
28
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of Denosumab on Cellular Biomarkers in the Human Breast
Baseline characteristics by cohort
| Measure |
No Treatment
n=27 Participants
Participants received no treatment and underwent percutaneous core needle breast biopsies on Day 1 and Day 28.
|
Denosumab 60 mg
n=27 Participants
Participants received 60 mg denosumab by subcutaneous injection on Day 1 and underwent percutaneous core needle breast biopsies on Day 1 and Day 28.
|
Denosumab 120 mg
n=28 Participants
Participants received 120 mg denosumab by subcutaneous injection on Day 1 and underwent percutaneous core needle breast biopsies on Day 1 and Day 28.
|
Total
n=82 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
29.9 years
STANDARD_DEVIATION 7.3 • n=5 Participants
|
32.2 years
STANDARD_DEVIATION 7.6 • n=7 Participants
|
32.8 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
32.5 years
STANDARD_DEVIATION 8.2 • n=4 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
82 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black (or African American)
|
4 participants
n=5 Participants
|
8 participants
n=7 Participants
|
10 participants
n=5 Participants
|
22 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Whte
|
21 participants
n=5 Participants
|
19 participants
n=7 Participants
|
16 participants
n=5 Participants
|
56 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 28Population: Pharmacodynamic analysis set with non-missing data
Ki-67 is a marker for cell proliferation. Participants underwent percutaneous core needle breast biopsies on Day 1 (Baseline, prior to treatment) and Day 28. Levels of Ki67 were measured using immunohistochemical staining and digital imaging. The proliferation index was calculated as the percentage of Ki-67 positive terminal ductal lobular unit (TDLU) and duct epithelial cells. The higher the percentage, the higher the rate of epithelial cell proliferation.
Outcome measures
| Measure |
No Treatment
n=25 Participants
Participants received no treatment and underwent percutaneous core needle breast biopsies on Day 1 and Day 28.
|
Denosumab 60 mg
n=25 Participants
Participants received 60 mg denosumab by subcutaneous injection on Day 1 and underwent percutaneous core needle breast biopsies on Day 1 and Day 28.
|
Denosumab 120 mg
n=26 Participants
Participants received 120 mg denosumab by subcutaneous injection on Day 1 and underwent percutaneous core needle breast biopsies on Day 1 and Day 28.
|
|---|---|---|---|
|
Log Ratio of Post-baseline to Baseline Ki-67 Index in Mammary Epithelial Cells
|
0.084 log ratio
Standard Deviation 0.645
|
-0.100 log ratio
Standard Deviation 1.048
|
-0.081 log ratio
Standard Deviation 0.918
|
Adverse Events
Treatment A No Treatment
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Treatment B 60 MG SC
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Treatment C 120 MG SC
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A No Treatment
n=27 participants at risk
Participants in this group received no treatment and underwent percutaneous core needle breast biopsies on Day 1 and Day 28.
|
Treatment B 60 MG SC
n=27 participants at risk
Participants received 60 mg denosumab by subcutaneous injection on Day 1 and underwent percutaneous core needle breast biopsies on Day 1 and Day 28.
|
Treatment C 120 MG SC
n=28 participants at risk
Participants received 120 mg denosumab by subcutaneous injection on Day 1 and underwent percutaneous core needle breast biopsies on Day 1 and Day 28.
|
|---|---|---|---|
|
General disorders
Injection site erythema
|
0.00%
0/27 • 28 days
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
3.7%
1/27 • 28 days
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
35.7%
10/28 • 28 days
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
14.8%
4/27 • 28 days
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
14.8%
4/27 • 28 days
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
7.1%
2/28 • 28 days
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Nervous system disorders
Headache
|
0.00%
0/27 • 28 days
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/27 • 28 days
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
7.1%
2/28 • 28 days
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Reproductive system and breast disorders
Breast haematoma
|
0.00%
0/27 • 28 days
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
7.4%
2/27 • 28 days
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/28 • 28 days
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
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