Trial Outcomes & Findings for Bexarotene in Preventing Breast Cancer in Patients at High Risk for Breast Cancer (NCT NCT03323658)
NCT ID: NCT03323658
Last Updated: 2023-01-10
Results Overview
Dose Limiting Toxicity (DLT) is defined as a grade 2 skin adverse event that persists for at least 6 days or any grade 3 or greater adverse event possibly, probably, or definitely related to the study drug. In addition, a DLT will be a grade 2 skin adverse event that recurs and persists for at least 3 days.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
Results posted on
2023-01-10
Participant Flow
Women at high risk for breast cancer were recruited for the trial at the Cancer Prevention Center at MD Anderson Cancer Center.
41 participants were consented, 17 were not randomized due to (1 )Dose escalation phase closed and (16) were not eligible.
Participant milestones
| Measure |
Dose Level 1
Bexarotene 1 % gel 10 mg every other day
|
Dose Level 2
Bexarotene 1 % gel 10 mg daily
|
Expansion Cohort
Bexarotene 1 % gel 10 mg every other day
|
|---|---|---|---|
|
Overall Study
STARTED
|
10
|
4
|
10
|
|
Overall Study
COMPLETED
|
10
|
3
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Dose Level 1
Bexarotene 1 % gel 10 mg every other day
|
Dose Level 2
Bexarotene 1 % gel 10 mg daily
|
Expansion Cohort
Bexarotene 1 % gel 10 mg every other day
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
Baseline Characteristics
Bexarotene in Preventing Breast Cancer in Patients at High Risk for Breast Cancer
Baseline characteristics by cohort
| Measure |
Dose Level 1
n=10 Participants
Bexarotene 1 % gel 10 mg every other day
|
Dose Level 2
n=4 Participants
Bexarotene 1 % gel 10 mg daily
|
Expansion Cohort
n=10 Participants
Bexarotene 1 % gel 10 mg every other day
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
40-49 years
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Age, Customized
50-59 years
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Age, Customized
60-69 years
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Age, Customized
70 and over years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
24 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
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 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
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
4 participants
n=7 Participants
|
10 participants
n=5 Participants
|
24 participants
n=4 Participants
|
|
Menopause
Pre-Menopausal
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Menopause
Post-Menopausal
|
8 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessmentsDose Limiting Toxicity (DLT) is defined as a grade 2 skin adverse event that persists for at least 6 days or any grade 3 or greater adverse event possibly, probably, or definitely related to the study drug. In addition, a DLT will be a grade 2 skin adverse event that recurs and persists for at least 3 days.
Outcome measures
| Measure |
Dose Level 1
n=10 Participants
Bexarotene 1 % gel 10 mg every other day.
|
Dose Level 2
n=4 Participants
Bexarotene 1 % gel 10 mg daily
|
Expansion Cohort
n=10 Participants
Bexarotene 1 % gel 10 mg every other day
|
|---|---|---|---|
|
Number of Participants With Incidence of Adverse Events (Dose Limiting Toxicities)
Maculopapular rash with pruritus at application site
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Incidence of Adverse Events (Dose Limiting Toxicities)
Erythema/redness at application site
|
0 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline up to 28 daysSerum biomarkers to be tested will be total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, thyroid-stimulating hormone, T4, T3, and calcium. Will be summarized using mean, standard deviation and median (range) for continuous variables at each time point. Wilcoxon rank-sum test may be used to examine the difference of continuous variables between participants' characteristics groups. Will be plotted as functions of time (baseline, week 1, week 2, and week 4). Linear mixed effect model will be applied to model the biomarker change over time for all participants. Appropriate transformation and regression model will be used to ensure the model fit.
Outcome measures
| Measure |
Dose Level 1
n=10 Participants
Bexarotene 1 % gel 10 mg every other day.
|
Dose Level 2
n=4 Participants
Bexarotene 1 % gel 10 mg daily
|
Expansion Cohort
n=10 Participants
Bexarotene 1 % gel 10 mg every other day
|
|---|---|---|---|
|
Number of Participants With Changes in Markers of Systemic Toxicity
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: baseline and end of treatment, up to 4 weeksPlasma concentrations of bexarotene were evaluated in all participants at baseline and at end of study. Plasma samples: ND = Not detected (below the quantitation limit of 0.5 ng/mL) TDL = Trace levels detected (below the LOQ of 0.5ng/mL; estimated value)
Outcome measures
| Measure |
Dose Level 1
n=10 Participants
Bexarotene 1 % gel 10 mg every other day.
|
Dose Level 2
n=4 Participants
Bexarotene 1 % gel 10 mg daily
|
Expansion Cohort
n=10 Participants
Bexarotene 1 % gel 10 mg every other day
|
|---|---|---|---|
|
Number of Participants With Trace Level of Bexarotene Concentration in Plasma Detected
Plasma Baseline Visit
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Trace Level of Bexarotene Concentration in Plasma Detected
Plasma End of Treatment Visit
|
0 Participants
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: end of treatment, up to 4 weeksPopulation: 1 participant was to analyzed.
Breast tissue concentrations were available only in those women who underwent breast biopsies. Tissue samples: Not detected (below the quantitation limit of 2.5 ng/g for a 10mg sample) and Trace levels detected (below the LOQ of 2.5ng/g; estimated value).
Outcome measures
| Measure |
Dose Level 1
n=5 Participants
Bexarotene 1 % gel 10 mg every other day.
|
Dose Level 2
n=1 Participants
Bexarotene 1 % gel 10 mg daily
|
Expansion Cohort
n=9 Participants
Bexarotene 1 % gel 10 mg every other day
|
|---|---|---|---|
|
Number of Participants With Bexarotene Concentration in Tissue
Non Detected
|
1 Participants
|
0 Participants
|
4 Participants
|
|
Number of Participants With Bexarotene Concentration in Tissue
Trace Levels Detected
|
1 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Bexarotene Concentration in Tissue
Quantitation limit of 2.6-10 ng/g
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Bexarotene Concentration in Tissue
Quantitation limit of 11-20 ng/g
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Bexarotene Concentration in Tissue
Quantitation limit of 21-30 ng/g
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Bexarotene Concentration in Tissue
Quantitation limit of >30 ng/g
|
0 Participants
|
0 Participants
|
1 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline, 15, and Day 28 visitsOne of the four cores collected from the core biopsies from baseline (in dose expansion cohort only) and post treatment (all dose expansion cohort participants and optional for dose escalation group) will be formalin-fixed and paraffin embedded (FFPE) for histological analysis. One of the four cores collected from the core biopsies from baseline and post treatment will be placed in RNALater and utilized for gene expression of ribonucleic acid (RNA) biomarkers. Gene expression will be performed.
Outcome measures
Outcome data not reported
Adverse Events
Dose Level 1
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Dose Level 2
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Expansion Cohort
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Dose Level 1
n=10 participants at risk
Bexarotene 1 % gel 10 mg every other day
|
Dose Level 2
n=4 participants at risk
Bexarotene 1 % gel 10 mg daily
|
Expansion Cohort
n=10 participants at risk
Bexarotene 1 % gel 10 mg every other day
|
|---|---|---|---|
|
Ear and labyrinth disorders
Motion Sickness
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Gastrointestinal disorders
Dyspepsia
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
General disorders
General Disorders and Administration Site Conditions-Other, Specify
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
General disorders
Tired(Fatigue)
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
25.0%
1/4 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
General disorders
Tongue Swelling/soreness
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Immune system disorders
Dermatitis (blistering)
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
25.0%
1/4 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Immune system disorders
Allergic reaction, small itchy lump on right arm at allergy shot injection site
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Infections and infestations
COVID-19
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Investigations
Absolute neutrophil count decreased
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Nervous system disorders
Headache
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Psychiatric disorders
Depression
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
25.0%
1/4 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Psychiatric disorders
Sleep disturbance/insomnia
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
25.0%
1/4 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Reproductive system and breast disorders
Breast Tenderness
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Reproductive system and breast disorders
Reproductive System and Breast Disorders-Other, Specify
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Respiratory, thoracic and mediastinal disorders
Cough/Coughing
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
25.0%
1/4 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Skin and subcutaneous tissue disorders
Pain of Skin
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Skin and subcutaneous tissue disorders
Rash Maculopapular
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Skin and subcutaneous tissue disorders
Skin and Subcutaneous Tissue Disorders - Other, Specify
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Skin and subcutaneous tissue disorders
Skin and Subcutaneous Tissue Disorders- Other, Specify
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
10.0%
1/10 • Number of events 1 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
20.0%
2/10 • Number of events 2 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/4 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
0.00%
0/10 • 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
|
Additional Information
Priya Thomas,MD-Associate Professor, Clinical Cancer Prevention
UT MD Anderson Cancer Center
Phone: (713) 745-1075
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60