Browse EPPT > MDA2016-08-02
A Phase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer

The following datasets contain the data available for EPPT MDA2016-08-02. The description and documentation for each file is listed below. SAS7bdat and CSV versions of the actual data will be available to CDAS projects approved to use this study's data.

Analysis Datasets

Files	Description
Data Dictionary (PDF - 54.5 KB)	1. The Adverse Events dataset contains adverse events that occurred during the study.
Data Dictionary (PDF - 884.3 KB)	2. The Enhanced Person dataset contains all relevant information from every dataset received (except adverse dataset). Each record represents one participant and contains updated variable names, formats, and labels. All information coming from non-person-based datasets has been converted into a person-based format.

Raw Datasets

These 38 datasets contain the raw form data received, excluding PII.

Show these datasets

Files	Description
Data Dictionary (PDF - 64.2 KB)	1. The Adverse Events dataset contains adverse events that occurred during the study.
Data Dictionary (PDF - 53.2 KB)	2. The Agent Modification dataset contains any modifications of the study agent during the study.
Data Dictionary (PDF - 121.0 KB)	3. The Baseline Alcohol dataset contains alcohol Assessment - Baseline
Data Dictionary (PDF - 49.2 KB)	4. The Baseline Medical/Surgical History dataset contains baseline Medical/Surgical History - Other Body System
Data Dictionary (PDF - 49.8 KB)	5. The Baseline Medical/Surgical History dataset contains baseline Medical/Surgical History
Data Dictionary (PDF - 48.8 KB)	6. The Baseline Symptoms dataset contains baseline Signs and Symptoms
Data Dictionary (PDF - 138.8 KB)	7. The Baseline Tobacco dataset contains tobacco Assessment - Baseline
Data Dictionary (PDF - 50.3 KB)	8. The Breast Imaging dataset contains breast Imaging
Data Dictionary (PDF - 57.0 KB)	9. The Clinical Lab - Blood Chemistry dataset contains clinical Laboratory Data Blood Chemistry - Results of blood tests and whether or not they were abnormal/out of range.
Data Dictionary (PDF - 54.2 KB)	10. The Clinical Lab - Hematology dataset contains clinical Laboratory Data Hematology - Lab Tests - Results of hematology tests and whether or not they were abnormal/out of range.
Data Dictionary (PDF - 54.2 KB)	11. The Clinical Lab - Hematology dataset contains clinical Laboratory Data Hematology - Differential Lab Tests - Results of hematology tests and whether or not they were abnormal/out of range.
Data Dictionary (PDF - 51.0 KB)	12. The Comments dataset contains any extra comments about a specific field on a form.
Data Dictionary (PDF - 62.0 KB)	13. The Compliance dataset contains information indicating whether participants were compliant with the study protocol.
Data Dictionary (PDF - 58.2 KB)	14. The Concomitant Medications dataset contains any concomitant medications taken throughout the study.
Data Dictionary (PDF - 64.6 KB)	15. The Dermatology dataset contains dermatology - Body System/Site
Data Dictionary (PDF - 63.2 KB)	16. The Dermatology dataset contains dermatology - Other Body System/Site
Data Dictionary (PDF - 53.4 KB)	17. The Dose Assignment/Intervention Admin dataset contains dose Assignment/Intervention Administration
Data Dictionary (PDF - 44.8 KB)	18. The Eligibility dataset contains eligibility Verification
Data Dictionary (PDF - 45.9 KB)	19. The Exclusion Criteria dataset contains exclusion Criteria
Data Dictionary (PDF - 48.8 KB)	20. The Family History dataset contains family History
Data Dictionary (PDF - 56.3 KB)	21. The Followup Alcohol dataset contains alcohol Assessment - Follow-Up
Data Dictionary (PDF - 126.4 KB)	22. The Followup Tobacco dataset contains tobacco Assessment - Follow-Up
Data Dictionary (PDF - 46.1 KB)	23. The Inclusion Criteria dataset contains inclusion Criteria
Data Dictionary (PDF - 105.4 KB)	24. The Off Study dataset contains reason each participant is off the study.
Data Dictionary (PDF - 73.5 KB)	25. The Physical Exam dataset contains physical Exam - Anthropometry information.
Data Dictionary (PDF - 73.4 KB)	26. The Physical Exam dataset contains physical Exam - Other Body System/Site
Data Dictionary (PDF - 50.4 KB)	27. The Pregnancy Test dataset contains pregnancy Specimen Data
Data Dictionary (PDF - 48.2 KB)	28. The Previous Intervention dataset contains previous Intervention - Previous Therapy
Data Dictionary (PDF - 51.2 KB)	29. The Previous Intervention dataset contains previous Intervention - Previous Therapy Listing
Data Dictionary (PDF - 75.8 KB)	30. The Registration dataset contains registration - Demographic and race information
Data Dictionary (PDF - 75.8 KB)	31. The Registration dataset contains registration - Demographic and participant method of payment
Data Dictionary (PDF - 54.1 KB)	32. The Reproductive History dataset contains reproductive History
Data Dictionary (PDF - 50.5 KB)	33. The Specimen Acquisition - Research Blood dataset contains specimen Acquisition Research Blood
Data Dictionary (PDF - 56.4 KB)	34. The Specimen Acquisition - Tissue Biopsy dataset contains specimen Acquisition Tissue
Data Dictionary (PDF - 55.9 KB)	35. The Study Specimen Shipping Form dataset contains study Specimen Shipping Form - Tissue
Data Dictionary (PDF - 55.8 KB)	36. The Study Specimen Shipping Form dataset contains study Specimen Shipping Form - Blood
Data Dictionary (PDF - 50.9 KB)	37. The Telephone Contact dataset contains telephone Contact
Data Dictionary (PDF - 43.5 KB)	38. The Verification dataset contains investigator verification information.

Trial Summary

This phase I trial studies the side effects and best dose of bexarotene in preventing breast cancer in patients at high risk for breast cancer. Bexarotene belongs to a class of drugs that are called rexinoids, and it may reduce the incidence of breast tumors.

Dose Escalation Group:

Participants are assigned to one of three different dose levels. The three dose cohorts are as follows:

• Dose 1: Bexarotene 1% gel 10 mg applied topically to one unaffected breast QOD x 4 weeks.
• Dose 2: Bexarotene 1% gel 10 mg applied topically to one unaffected breast QOD x 7 days, then QD x 3 weeks.
• Dose 3: Bexarotene 1% gel 10 mg applied topically to one unaffected breast QOD x 7 days, then 10 mg QD x 1 week, then 20 mg QD x 2 weeks.

A conservative modification of the standard "3+3" design is applied. The first three participants are assigned to the lowest dose level (dose 1). New cohorts of 3-4 participants are not treated until toxicity is evaluated for all current participants for 4 weeks. After 10 participants have successfully completed the 4 weeks, the next cohort is assigned to the next dose level.

After completion of study treatment, patients are followed up at 30 days.

Dose Expansion Group:

An additional 10 participants are enrolled and treated at the maximum tolerated dose (dosing level that had 10 participants complete successfully) to further evaluate safety and drug penetration into the breast tissue. There is a ramp up to the desired dose similar to the ramp up schedule in the dose escalation group. All participants in the dose expansion cohort will have a core breast biopsy at baseline and end of treatment.

After completion of study treatment, patients are followed up at 30 days.

Enrollment Statistics

Target Enrollment: 41

Actual Enrollment: 24

Actual Registration: 24

• 24 people selected
  • 10 in the Dose Escalation Cohort, Dose 1 (10 out of 24 selected): Bexarotene 1% gel 10 mg applied topically to one unaffected breast QOD x 4 weeks
    • 10 completed the study.)
  • 4 in Dose Escalation Group, Dose 2 (4 out of 24 selected): Bexarotene 1% gel 10 mg applied topically to one unaffected breast QOD x 7 days, then QD x 3 weeks.
    • 3 completed the study.
    • 1 lost due to adverse events.
  • 10 in the Dose Expansion Cohort, Dose 1 (10 out of 24 selected): Bexarotene 1% gel 10 mg applied topically to one unaffected breast QOD x 4 weeks
    • 10 completed the study.
• 17 people were not selected (17 of 41 registered)
  • 1 dose escalation phase closed.
  • 16 were not eligible.

Statistical Analysis and Total Study Population Demographics:

• Age (years):
  • 40-49: 12.5% (N=3)
  • 50-59: 37.5% (N=9)
  • 60-69: 41.7% (N=10)
  • >=70: 8.3% (N=3)
• Height (cm):
  • Mean: 161
  • IQR: 158 - 164
  • Range: 146 - 175
  • Median: 162
• Weight (kg):
  • Mean: 77
  • IQR: 67 - 88
  • Range: 54 - 103
  • Median: 75
• Gender
  • Females: 24 (100%)

Eligibility Criteria

Inclusion Criteria

• Participants must be at high risk as defined by a history of breast cancer (invasive or ductal breast carcinoma in situ [DCIS]) and be at least 5 years out from diagnosis, or lobular carcinoma in situ (LCIS), or proliferative benign breast disease such atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH) or genetic test confirmation of BRCA 1/2 mutation carrier or have a breast cancer risk assessment >= 1.7% in 5 years or a lifetime risk >= 20%
• No evidence of disease (in situ or invasive cancer that would normally be treated by resection) at trial entry as determined by the investigator; diagnosis of invasive cancer must be at least 5 years prior to initiation on trial
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
• Leukocytes >= 3,000/microliter
• Absolute neutrophil count >= 1,500/microliter
• Platelets >= 100,000/microliter
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional upper limit of normal (ULN)
• Creatinine =< 1.5 x institutional ULN
• Hemoglobin >= 10 g/dL
• Thyroid-stimulating hormone (TSH) within normal institutional limits
• Triglycerides =< 300 mg/dl
• Total cholesterol =< 300 mg/dl
• >= 6 months from all previous breast cancer treatment (including endocrine therapy)
• Participants must have adequate accessible breast tissue as determined by the treating physician, consisting of one breast unaffected by invasive cancer, which has not been radiated; a history of benign core biopsy of this breast will be permitted.
• Participants need to have had any breast imaging with a normal/benign (bi-rads 1 or 2) result within 180 days of day 0 and no further routine breast imaging planned during the course of the study (4 weeks); exception: if the mammogram result was a bi-rads 0 and the imaging work-up (ultrasound and/or magnetic resonance imaging [MRI]) result comes back normal/benign (bi-rads 1 or 2) before treatment initiation, then participant is eligible.
• For women of childbearing potential; negative pregnancy testing within 72 hours prior to or on study visit #1 (day 0) and willingness to use adequate contraception during the study intervention; OR post-menopausal defined as any one of the following 1) prior hysterectomy, 2) absence of menstrual period for 1 year in the absence of prior chemotherapy or 3) absence of menstrual period for 2 years in women with a prior history of chemotherapy exposure who were pre-menopausal prior to chemotherapy; in women of childbearing potential, effective contraception must be used for one month prior to the initiation of therapy, during therapy, and for at least one month following discontinuation of therapy; it is recommended that two reliable forms of contraception be used simultaneously; if participants are interested in enrolling and have not met the requirement for contraception, they will be seen in the clinic in 1 month for re-evaluation once they have met this requirement and ensure all other eligibility criteria is met prior to dose assignment
• Willingness to comply with all study interventions and follow-up procedures including the ability to apply the study drug to the breast
• Ability to understand and the willingness to sign a written informed consent document
• Ability to avoid exposure of the treated breast area to sunlight and artificial ultraviolet light during the use of bexarotene gel

Exclusion Criteria

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to bexarotene gel, oral or topical retinoids
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, thromboembolic disease, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant, or had given birth, or nursed at any time during the last 12 months
• Women with a history of any cancer within the last 3 years, except for non-melanoma skin cancer; history of breast cancer must be at least > 5 years from diagnosis
• Prior bilateral breast surgery (mastectomy, segmental mastectomy, or breast augmentation surgery including breast implants or breast reductions) or combination of breast radiation and surgery involving both breasts
• Prior history or evidence of metastatic breast cancer
• Prior history of histologically confirmed bilateral invasive breast cancer
• Current use or < 6 months since use of selective estrogen receptor modulator (SERMS) or aromatase inhibitors or any other investigational treatment for breast cancer prevention or therapy
• Skin lesions that disrupt the stratum corneum (e.g., eczema, ulceration) or any breakdown of the skin
• Current use of a retinol containing agent or any retinoid analogue drug within the last 30 days
• Dietary vitamin A intake >= 5,000 IU/day (as determined by dietary supplementation)
• Treatment with any investigational drug or investigational biologic within 30 days of initiating study treatment or during the study
• History of human immunodeficiency virus (HIV) or active hepatitis C

The Schema is a timeline of the study. It indicates start/end points, visits expected, major testing to be done, and any other information that is crucial to understanding how the study was completed.

Schema

Results/Findings:

Study participants

A total of 41 women consented to the study; 24 were assigned to a dose level in either the dose escalation or dose expansion phase. The main reasons for ineligibility were abnormalities in baseline labs such as elevated cholesterol, triglycerides, and elevated liver function enzymes. Ten women were enrolled at dose level 1 and no DLTs were noted with every other day dosing. Therefore, enrollment continued to dose level 2, 10 mg daily dosing, and 4 participants were enrolled at this dose. Two participants experienced DLTs and thus no further participants were enrolled at this dose level per protocol stopping rules. No participants were enrolled at dose level 3 (20 mg daily). MTD was determined to be the every other day dosing regimen and, therefore, the dose expansion phase enrolled an additional 10 women at this dose level. All women were compliant with study gel application.