Trial Outcomes & Findings for Prevention Strategy for Pre-Menopausal Women at High Risk for Development of Breast Cancer (NCT NCT01276704)
NCT ID: NCT01276704
Last Updated: 2023-09-21
Results Overview
Change over the course of study in the percent of breast epithelial cells expressing the proliferation marker Ki- 67/MIB-1 in hyperplastic benign breast tissue acquired by random periareolar fine needle aspiration pre-study and post-study.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
180 participants
Primary outcome timeframe
12 months
Results posted on
2023-09-21
Participant Flow
180 participants were screened and found to be eligible. Two withdrew consent prior to being randomized. Of the 178 randomized, 116 were assigned to active agent; 62 to placebo. One active agent participant withdrew prior to receiving study agent. The 177 who received study agent constitute the analytic population.
Participant milestones
| Measure |
Flaxseed Lignan, SDG
Secoisolariciresinol diglycoside
secoisolariciresinol: 1 capsule daily of secoisolariciresinol diglycoside (SDG)50mg
|
Placebo
Matched Placebo
Placebo: The placebo contains same filler materials as commercially available Brevail® but without active SDG.
|
|---|---|---|
|
Overall Study
STARTED
|
115
|
62
|
|
Overall Study
COMPLETED
|
101
|
51
|
|
Overall Study
NOT COMPLETED
|
14
|
11
|
Reasons for withdrawal
| Measure |
Flaxseed Lignan, SDG
Secoisolariciresinol diglycoside
secoisolariciresinol: 1 capsule daily of secoisolariciresinol diglycoside (SDG)50mg
|
Placebo
Matched Placebo
Placebo: The placebo contains same filler materials as commercially available Brevail® but without active SDG.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
3
|
|
Overall Study
Non-compliant
|
2
|
2
|
|
Overall Study
Withdrawal by Subject
|
7
|
1
|
|
Overall Study
Physician Decision
|
3
|
5
|
Baseline Characteristics
Prevention Strategy for Pre-Menopausal Women at High Risk for Development of Breast Cancer
Baseline characteristics by cohort
| Measure |
Flaxseed Lignan, SDG
n=115 Participants
Secoisolariciresinol diglycoside
secoisolariciresinol: 1 capsule daily of secoisolariciresinol diglycoside (SDG)50mg
|
Placebo
n=62 Participants
Matched Placebo
Placebo: The placebo contains same filler materials as commercially available Brevail® but without active SDG.
|
Total
n=177 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.4 years
STANDARD_DEVIATION 6.7 • n=99 Participants
|
39.7 years
STANDARD_DEVIATION 6.1 • n=107 Participants
|
38.8 years
STANDARD_DEVIATION 6.5 • n=206 Participants
|
|
Sex: Female, Male
Female
|
115 Participants
n=99 Participants
|
62 Participants
n=107 Participants
|
177 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
108 Participants
n=99 Participants
|
60 Participants
n=107 Participants
|
168 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
103 Participants
n=99 Participants
|
59 Participants
n=107 Participants
|
162 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
115 participants
n=99 Participants
|
62 participants
n=107 Participants
|
177 participants
n=206 Participants
|
|
Ki-67 expression
|
6.1 percent of breast epithelial cells
STANDARD_DEVIATION 0.4 • n=99 Participants
|
5.4 percent of breast epithelial cells
STANDARD_DEVIATION 4.2 • n=107 Participants
|
5.9 percent of breast epithelial cells
STANDARD_DEVIATION 4.4 • n=206 Participants
|
PRIMARY outcome
Timeframe: 12 monthsChange over the course of study in the percent of breast epithelial cells expressing the proliferation marker Ki- 67/MIB-1 in hyperplastic benign breast tissue acquired by random periareolar fine needle aspiration pre-study and post-study.
Outcome measures
| Measure |
Flaxseed Lignan, SDG
n=101 Participants
Secoisolariciresinol diglycoside
secoisolariciresinol: 1 capsule daily of secoisolariciresinol diglycoside (SDG)50mg
|
Placebo
n=51 Participants
Matched Placebo
Placebo: The placebo contains same filler materials as commercially available Brevail® but without active SDG.
|
|---|---|---|
|
Change in Percent of Breast Epithelial Cells With Ki-67 Immunocytochemical Expression
|
-1.4 change in percent Ki-67
Standard Deviation 5.3
|
-1.4 change in percent Ki-67
Standard Deviation 5.3
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Adequate residual material available from baseline and 12-month specimens for post-hoc analysis of change in gene expression.
Gene expression in breast epithelial cells assessed by RT-qPCR. Change in expression (fold-change for 12-months compared to baseline value) was evaluated by cluster analysis and used to define "responders" and non-responders" based on favorable or non-favorable modulation of a set of 12 relevant genes. Specifically, data for change in ESR1 (codes for estrogen receptor alpha) are shown.
Outcome measures
| Measure |
Flaxseed Lignan, SDG
n=49 Participants
Secoisolariciresinol diglycoside
secoisolariciresinol: 1 capsule daily of secoisolariciresinol diglycoside (SDG)50mg
|
Placebo
n=28 Participants
Matched Placebo
Placebo: The placebo contains same filler materials as commercially available Brevail® but without active SDG.
|
|---|---|---|
|
Change in Gene Expression
No substantial change
|
36 Participants
|
19 Participants
|
|
Change in Gene Expression
> 2-fold increase
|
3 Participants
|
7 Participants
|
|
Change in Gene Expression
< 0.5 fold change
|
10 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 12 monthsQuality of life as measured by the Breast Cancer Prevention Trial (BCPT) Symptom Checklist, completed at baseline and end of study by each participant. Responses to 43 questions (with each question given a value from 0 to 4, higher score being worse) are clustered into seven domains to yield an average score per domain. These seven category scores are then averaged to provide a final average score (range by definition, 0 to 4). Change in score over the course of the intervention per individual is then assessed. By definition, change in score theoretically ranges from -4 to +4.
Outcome measures
| Measure |
Flaxseed Lignan, SDG
n=101 Participants
Secoisolariciresinol diglycoside
secoisolariciresinol: 1 capsule daily of secoisolariciresinol diglycoside (SDG)50mg
|
Placebo
n=51 Participants
Matched Placebo
Placebo: The placebo contains same filler materials as commercially available Brevail® but without active SDG.
|
|---|---|---|
|
Breast Cancer Prevention Trial (BCPT) Symptom Checklist
|
-0.05 Change in score on a scale
Interval -2.3 to 1.4
|
0.21 Change in score on a scale
Interval -1.4 to 2.7
|
Adverse Events
Flaxseed Lignan, SDG
Serious events: 2 serious events
Other events: 84 other events
Deaths: 0 deaths
Placebo
Serious events: 4 serious events
Other events: 45 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Flaxseed Lignan, SDG
n=115 participants at risk
Secoisolariciresinol diglycoside
secoisolariciresinol: 1 capsule daily of secoisolariciresinol diglycoside (SDG)50mg
|
Placebo
n=62 participants at risk
Matched Placebo
Placebo: The placebo contains same filler materials as commercially available Brevail® but without active SDG.
|
|---|---|---|
|
Nervous system disorders
vestibular disorder
|
0.00%
0/115 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
1.6%
1/62 • Number of events 1 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
|
Musculoskeletal and connective tissue disorders
musculoskeletal connective tissue disorder
|
0.00%
0/115 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
1.6%
1/62 • Number of events 1 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
|
Ear and labyrinth disorders
sinus disorder
|
0.00%
0/115 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
1.6%
1/62 • Number of events 1 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast abnormality
|
0.00%
0/115 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
1.6%
1/62 • Number of events 1 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
|
Gastrointestinal disorders
Nausea
|
0.87%
1/115 • Number of events 1 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
0.00%
0/62 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
|
Pregnancy, puerperium and perinatal conditions
Unintended pregnancy
|
0.87%
1/115 • Number of events 1 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
0.00%
0/62 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
Other adverse events
| Measure |
Flaxseed Lignan, SDG
n=115 participants at risk
Secoisolariciresinol diglycoside
secoisolariciresinol: 1 capsule daily of secoisolariciresinol diglycoside (SDG)50mg
|
Placebo
n=62 participants at risk
Matched Placebo
Placebo: The placebo contains same filler materials as commercially available Brevail® but without active SDG.
|
|---|---|---|
|
Product Issues
Grade 1 AE
|
31.3%
36/115 • Number of events 36 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
27.4%
17/62 • Number of events 17 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
|
Product Issues
Grade 2 AE
|
33.9%
39/115 • Number of events 39 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
38.7%
24/62 • Number of events 24 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
|
Product Issues
Grade 3 AE
|
7.8%
9/115 • Number of events 9 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
12.9%
8/62 • Number of events 8 • 12 months
When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.
|
Additional Information
Bruce F. Kimler, Ph.D.
University of Kansas Medical Center
Phone: 913-205-6382
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place