A Phase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer
Overview
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Number of Participants With Incidence of Adverse Events (Dose Limiting Toxicities)
Overview
Brief 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.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the recommended phase II dose of topical bexarotene 1% (weight by weight [w/w]) gel for evaluation in healthy women. (Dose Escalation Group) II. Conduct an intervention of topical 1% bexarotene gel to an unaffected breast of healthy women at high risk for breast cancer for 4 weeks at the maximum tolerated dose (MTD) as determined during the dose escalation group phase to assess bexarotene concentration in the breast tissue. (Dose Expansion Group)
SECONDARY OBJECTIVES:
I. To detect bexarotene concentration in the serum at baseline and at 4 weeks of treatment.
II. To detect bexarotene concentration in the breast tissue at 4 weeks of treatment in the dose escalation group.
III. To investigate the effects of topical bexarotene on serum biomarkers, we will determine the change from baseline in i) lipid biomarkers (total cholesterol, triglycerides, low density lipoprotein [LDL], high density lipoprotein [HDL]), ii) thyroid function biomarkers (thyroid stimulating hormone [TSH], T4, T3), iii) calcium.
EXPLORATORY OBJECTIVE:
I. To examine changes in gene expression associated with retinoid action. (Dose Expansion Group)
OUTLINE: This is a dose-escalation study.
Group 1 will apply 10mg bexarotene topically to one breast every other day (QOD) for 4 weeks; Group 2 will apply 10mg bexarotene topically to one breast every other day (QOD) for 1 week and then daily for 3 weeks after confirmation that toxicity is at an acceptable range; Group 3 will apply 10mg bexarotene topically to one breast every other day (QOD) for 1 week, then daily for 1 week, and then 20mg daily for 2 weeks after confirmation that toxicity is at an acceptable range.
After completion of study treatment, patients are followed up at 30 days.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
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
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
Arms & Interventions
Prevention (bexarotene)
Group 1 will apply 10mg bexarotene topically to one breast QOD for 4 weeks; Group 2 will apply 10mg bexarotene topically to one breast QOD for 1 week and then daily for 3 weeks after confirmation that toxicity is at an acceptable range; Group 3 will apply 10mg bexarotene topically to one breast QOD for 1 week, then daily for 1 week, and then 20mg daily for 2 weeks after confirmation that toxicity is at an acceptable range.
Intervention: Bexarotene (Drug)
Prevention (bexarotene)
Group 1 will apply 10mg bexarotene topically to one breast QOD for 4 weeks; Group 2 will apply 10mg bexarotene topically to one breast QOD for 1 week and then daily for 3 weeks after confirmation that toxicity is at an acceptable range; Group 3 will apply 10mg bexarotene topically to one breast QOD for 1 week, then daily for 1 week, and then 20mg daily for 2 weeks after confirmation that toxicity is at an acceptable range.
Intervention: Questionnaire Administration (Other)
Outcomes
Primary Outcomes
Number of Participants With Incidence of Adverse Events (Dose Limiting Toxicities)
Time Frame: 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
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.
Secondary Outcomes
- Number of Participants With Bexarotene Concentration in Tissue(end of treatment, up to 4 weeks)
- Number of Participants With Changes in Markers of Systemic Toxicity(Baseline up to 28 days)
- Number of Participants With Trace Level of Bexarotene Concentration in Plasma Detected(baseline and end of treatment, up to 4 weeks)