Trial Outcomes & Findings for Testing an Active Form of Tamoxifen (4-hydroxytamoxifen) Delivered Through Breast Skin to Control Ductal Carcinoma in Situ (DCIS) of the Breast (NCT NCT02993159)
NCT ID: NCT02993159
Last Updated: 2024-12-18
Results Overview
Change in the Ki-67 labelling index of DCIS lesions evaluated using immunohistochemistry
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
100 participants
Primary outcome timeframe
baseline to up to 10 weeks
Results posted on
2024-12-18
Participant Flow
Participant milestones
| Measure |
Arm I (4-OHT Topical Gel, Placebo)
2mg 4-hydroxytamoxifen (4-OHT) topical gel applied once daily per breast and placebo PO daily for 4-10 weeks
|
Arm II (Placebo, Oral Tamoxifen)
placebo gel applied once daily per breast and 20mg oral tamoxifen citrate PO daily for 4-10 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
47
|
53
|
|
Overall Study
COMPLETED
|
42
|
48
|
|
Overall Study
NOT COMPLETED
|
5
|
5
|
Reasons for withdrawal
| Measure |
Arm I (4-OHT Topical Gel, Placebo)
2mg 4-hydroxytamoxifen (4-OHT) topical gel applied once daily per breast and placebo PO daily for 4-10 weeks
|
Arm II (Placebo, Oral Tamoxifen)
placebo gel applied once daily per breast and 20mg oral tamoxifen citrate PO daily for 4-10 weeks
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
3
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Opted out of surgery
|
2
|
0
|
|
Overall Study
Surgery postponed due to COVID-19 and started AI
|
1
|
1
|
|
Overall Study
Physician Decision
|
0
|
1
|
Baseline Characteristics
Testing an Active Form of Tamoxifen (4-hydroxytamoxifen) Delivered Through Breast Skin to Control Ductal Carcinoma in Situ (DCIS) of the Breast
Baseline characteristics by cohort
| Measure |
Arm I (4-OHT Topical Gel, Placebo)
n=47 Participants
2mg 4-hydroxytamoxifen (4-OHT) topical gel applied once daily per breast and placebo PO daily for 4-10 weeks
|
Arm II (Placebo, Oral Tamoxifen)
n=53 Participants
placebo gel applied once daily per breast and 20mg oral tamoxifen citrate PO daily for 4-10 weeks
|
Total
n=100 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
38 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
47 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
42 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
12 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
31 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
65 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
47 participants
n=5 Participants
|
53 participants
n=7 Participants
|
100 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: baseline to up to 10 weeksPopulation: Participants with DCIS tissue samples at baseline and post-therapy
Change in the Ki-67 labelling index of DCIS lesions evaluated using immunohistochemistry
Outcome measures
| Measure |
Arm I (4-OHT Topical Gel, Placebo)
n=35 Participants
2mg 4-hydroxytamoxifen (4-OHT) topical gel applied once daily per breast and placebo PO daily for 4-10 weeks
|
Arm II (Placebo, Oral Tamoxifen)
n=40 Participants
placebo gel applied once daily per breast and 20mg oral tamoxifen citrate PO daily for 4-10 weeks
|
|---|---|---|
|
Change in Ki-67 Labeling Index
|
-1.0 percent positive cells
Interval -2.4 to 0.52
|
-4.8 percent positive cells
Interval -6.6 to -3.1
|
SECONDARY outcome
Timeframe: baseline to up to 10 weeksPopulation: Participants with Oncotype-DCIS score at baseline and post-therapy
Change in Exact Sciences Oncotype Diagnosis Breast Ductal Carcinoma in Situ Score (Oncotype DCIS-Score), a clinical validated clinically validated, commercially available genomic test for patients with DCIS. Oncotype DCIS-Score Range is 0-100. A negative change in scores indicates a lower risk of recurrence (better outcome).
Outcome measures
| Measure |
Arm I (4-OHT Topical Gel, Placebo)
n=32 Participants
2mg 4-hydroxytamoxifen (4-OHT) topical gel applied once daily per breast and placebo PO daily for 4-10 weeks
|
Arm II (Placebo, Oral Tamoxifen)
n=28 Participants
placebo gel applied once daily per breast and 20mg oral tamoxifen citrate PO daily for 4-10 weeks
|
|---|---|---|
|
Change in Oncotype DCIS-Score
|
-1.8 score on a scale
Interval -5.8 to 2.3
|
-16 score on a scale
Interval -22.0 to -9.4
|
SECONDARY outcome
Timeframe: up to 10 weeksPopulation: Participants with post-therapy tissue samples
Post-therapy concentrations of 4-OHT and endoxifen in breast tissue samples
Outcome measures
| Measure |
Arm I (4-OHT Topical Gel, Placebo)
n=40 Participants
2mg 4-hydroxytamoxifen (4-OHT) topical gel applied once daily per breast and placebo PO daily for 4-10 weeks
|
Arm II (Placebo, Oral Tamoxifen)
n=47 Participants
placebo gel applied once daily per breast and 20mg oral tamoxifen citrate PO daily for 4-10 weeks
|
|---|---|---|
|
Post-therapy Breast Tissue Levels of Tamoxifen and Its Metabolites
4-OHT, Superficial tissue sample
|
4.2 ng/g
Interval 1.5 to 17.8
|
6.0 ng/g
Interval 3.9 to 8.5
|
|
Post-therapy Breast Tissue Levels of Tamoxifen and Its Metabolites
4-OHT, Deep tissue sample
|
0.3 ng/g
Interval 0.0 to 0.3
|
13 ng/g
Interval 8.9 to 20.6
|
|
Post-therapy Breast Tissue Levels of Tamoxifen and Its Metabolites
Endoxifen, Superficial tissue sample
|
0.2 ng/g
Interval 0.2 to 0.3
|
16 ng/g
Interval 9.5 to 20.7
|
SECONDARY outcome
Timeframe: up to 10 weeksPopulation: Participants with post-therapy plasma samples
Post-therapy concentrations of 4-OHT and endoxifen in plasma samples
Outcome measures
| Measure |
Arm I (4-OHT Topical Gel, Placebo)
n=39 Participants
2mg 4-hydroxytamoxifen (4-OHT) topical gel applied once daily per breast and placebo PO daily for 4-10 weeks
|
Arm II (Placebo, Oral Tamoxifen)
n=47 Participants
placebo gel applied once daily per breast and 20mg oral tamoxifen citrate PO daily for 4-10 weeks
|
|---|---|---|
|
Post-therapy Plasma Levels of Tamoxifen and Its Metabolites
4-OHT, Plasma
|
0.2 ng/ml
Interval 0.1 to 0.4
|
2.0 ng/ml
Interval 1.4 to 2.7
|
|
Post-therapy Plasma Levels of Tamoxifen and Its Metabolites
Endoxifen, Plasma
|
0.0 ng/ml
Interval 0.0 to 0.0
|
10.5 ng/ml
Interval 6.4 to 13.8
|
SECONDARY outcome
Timeframe: baseline to up to 10 weeksPopulation: Participants with terminal duct lobular units (TDLUs) at baseline and post-therapy
Mean change in Ki-67 labelling index in the terminal duct lobular units (TDLUs)
Outcome measures
| Measure |
Arm I (4-OHT Topical Gel, Placebo)
n=16 Participants
2mg 4-hydroxytamoxifen (4-OHT) topical gel applied once daily per breast and placebo PO daily for 4-10 weeks
|
Arm II (Placebo, Oral Tamoxifen)
n=19 Participants
placebo gel applied once daily per breast and 20mg oral tamoxifen citrate PO daily for 4-10 weeks
|
|---|---|---|
|
Ki-67 Labelling Index in the Terminal Duct Lobular Units (TDLUs)
|
-0.11 percent positive
Interval -1.2 to 0.98
|
0.16 percent positive
Interval -0.67 to 0.99
|
SECONDARY outcome
Timeframe: baseline to up to 10 weeksPopulation: Participants with plasma samples at baseline and post-therapy
Mean change in percentage of plasma proteins involved in coagulation: Factor VIII, Factor IX, von Willebrand Factor, and total protein S
Outcome measures
| Measure |
Arm I (4-OHT Topical Gel, Placebo)
n=40 Participants
2mg 4-hydroxytamoxifen (4-OHT) topical gel applied once daily per breast and placebo PO daily for 4-10 weeks
|
Arm II (Placebo, Oral Tamoxifen)
n=48 Participants
placebo gel applied once daily per breast and 20mg oral tamoxifen citrate PO daily for 4-10 weeks
|
|---|---|---|
|
Change in Plasma Proteins Involved in Coagulation
Factor VIII
|
-0.50 percent
Interval -12.0 to 11.0
|
-8.8 percent
Interval -19.0 to 1.5
|
|
Change in Plasma Proteins Involved in Coagulation
Factor IX
|
0.07 percent
Interval -7.4 to 7.6
|
2.2 percent
Interval -2.0 to 6.4
|
|
Change in Plasma Proteins Involved in Coagulation
vWF
|
14 percent
Interval -5.5 to 34.0
|
30 percent
Interval 16.0 to 44.0
|
|
Change in Plasma Proteins Involved in Coagulation
Factor S
|
-2.9 percent
Interval -7.7 to 1.9
|
-11 percent
Interval -17.0 to -4.9
|
SECONDARY outcome
Timeframe: baseline to up to 10 weeksPopulation: Participants with plasma samples at baseline and post-therapy
Mean change in plasma markers of systemic estrogenic effect: SHBG.
Outcome measures
| Measure |
Arm I (4-OHT Topical Gel, Placebo)
n=40 Participants
2mg 4-hydroxytamoxifen (4-OHT) topical gel applied once daily per breast and placebo PO daily for 4-10 weeks
|
Arm II (Placebo, Oral Tamoxifen)
n=48 Participants
placebo gel applied once daily per breast and 20mg oral tamoxifen citrate PO daily for 4-10 weeks
|
|---|---|---|
|
Change in Plasma Markers of Systemic Estrogenic Effect (SHBG)
|
-0.24 nmol/l
Interval -10.0 to 9.9
|
15 nmol/l
Interval 4.5 to 25.0
|
SECONDARY outcome
Timeframe: baseline to up to 10 weeksPopulation: Participants with plasma samples at baseline and post-therapy
Mean change in plasma markers of systemic estrogenic effect: IGF-1
Outcome measures
| Measure |
Arm I (4-OHT Topical Gel, Placebo)
n=40 Participants
2mg 4-hydroxytamoxifen (4-OHT) topical gel applied once daily per breast and placebo PO daily for 4-10 weeks
|
Arm II (Placebo, Oral Tamoxifen)
n=48 Participants
placebo gel applied once daily per breast and 20mg oral tamoxifen citrate PO daily for 4-10 weeks
|
|---|---|---|
|
Change in Plasma Markers of Systemic Estrogenic Effect (IGF-1)
|
-1.2 ng/ml
Interval -9.8 to 7.4
|
-48 ng/ml
Interval -56.0 to -40.0
|
SECONDARY outcome
Timeframe: baseline to up to 10 weeksPopulation: Participants with BESS scores at baseline and post-therapy
Mean change in symptoms as captured using the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) questionnaire. A patient reported outcome, scores range from 0 (Not at All) to 4 (Extremely) when asked about experiencing symptoms. A positive change in scores indicates an increase in symptoms experienced and a negative change in scores indicates a decrease in symptoms experienced
Outcome measures
| Measure |
Arm I (4-OHT Topical Gel, Placebo)
n=32 Participants
2mg 4-hydroxytamoxifen (4-OHT) topical gel applied once daily per breast and placebo PO daily for 4-10 weeks
|
Arm II (Placebo, Oral Tamoxifen)
n=36 Participants
placebo gel applied once daily per breast and 20mg oral tamoxifen citrate PO daily for 4-10 weeks
|
|---|---|---|
|
Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire and Skin Reactions to 4-OHT Gel.
Vaginal
|
-0.03 score on a scale
Interval -0.23 to 0.16
|
-0.18 score on a scale
Interval -0.4 to 0.04
|
|
Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire and Skin Reactions to 4-OHT Gel.
Cognitive
|
0.09 score on a scale
Interval -0.09 to 0.27
|
-0.31 score on a scale
Interval -0.65 to 0.04
|
|
Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire and Skin Reactions to 4-OHT Gel.
Body Pain
|
-0.10 score on a scale
Interval -0.33 to 0.12
|
-0.15 score on a scale
Interval -0.37 to 0.08
|
|
Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire and Skin Reactions to 4-OHT Gel.
Vasomotor
|
0.15 score on a scale
Interval -0.08 to 0.37
|
0.53 score on a scale
Interval 0.23 to 0.82
|
|
Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire and Skin Reactions to 4-OHT Gel.
Gastrointestinal
|
-0.05 score on a scale
Interval -0.13 to 0.02
|
-0.06 score on a scale
Interval -0.15 to 0.04
|
|
Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire and Skin Reactions to 4-OHT Gel.
Sexual problems
|
0.14 score on a scale
Interval -0.55 to 0.83
|
-0.04 score on a scale
Interval -0.48 to 0.4
|
|
Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire and Skin Reactions to 4-OHT Gel.
Bladder
|
-0.06 score on a scale
Interval -0.3 to 0.18
|
-0.29 score on a scale
Interval -0.53 to -0.05
|
|
Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire and Skin Reactions to 4-OHT Gel.
Body image
|
0.04 score on a scale
Interval -0.03 to 0.11
|
-0.04 score on a scale
Interval -0.12 to 0.04
|
|
Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire and Skin Reactions to 4-OHT Gel.
Problem
|
-0.01 score on a scale
Interval -0.06 to 0.04
|
-0.04 score on a scale
Interval -0.11 to 0.04
|
Adverse Events
Arm I (4-OHT Topical Gel, Placebo)
Serious events: 0 serious events
Other events: 27 other events
Deaths: 0 deaths
Arm II (Placebo, Oral Tamoxifen)
Serious events: 0 serious events
Other events: 33 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm I (4-OHT Topical Gel, Placebo)
n=47 participants at risk
2mg 4-hydroxytamoxifen (4-OHT) topical gel applied once daily per breast and placebo PO daily for 4-10 weeks
|
Arm II (Placebo, Oral Tamoxifen)
n=53 participants at risk
placebo gel applied once daily per breast and 20mg oral tamoxifen citrate PO daily for 4-10 weeks
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
4.3%
2/47 • Number of events 47 • up to 10 weeks
|
11.3%
6/53 • Number of events 53 • up to 10 weeks
|
|
General disorders
Fatigue
|
8.5%
4/47 • Number of events 4 • up to 10 weeks
|
9.4%
5/53 • Number of events 6 • up to 10 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.4%
3/47 • Number of events 3 • up to 10 weeks
|
1.9%
1/53 • Number of events 1 • up to 10 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
4.3%
2/47 • Number of events 2 • up to 10 weeks
|
7.5%
4/53 • Number of events 4 • up to 10 weeks
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/47 • up to 10 weeks
|
5.7%
3/53 • Number of events 3 • up to 10 weeks
|
|
Reproductive system and breast disorders
Breast Pain
|
8.5%
4/47 • Number of events 4 • up to 10 weeks
|
0.00%
0/53 • up to 10 weeks
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
17.0%
8/47 • Number of events 9 • up to 10 weeks
|
15.1%
8/53 • Number of events 8 • up to 10 weeks
|
|
Vascular disorders
Hot flashes
|
34.0%
16/47 • Number of events 18 • up to 10 weeks
|
39.6%
21/53 • Number of events 25 • up to 10 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place