Houston, Texas 77030


Purpose:

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.


Study summary:

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. IV. To investigate the biologic effects of topical bexarotene 1% gel in the breast tissue, 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. TERTIARY OBJECTIVES: 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.


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 (eg., 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


NCT ID:

NCT03323658


Primary Contact:

Principal Investigator
Parijatham (Priya) S Thomas
M.D. Anderson Cancer Center


Backup Contact:

N/A


Location Contact:

Houston, Texas 77030
United States

Parijatham (Priya) S. Thomas
Phone: 713-745-1075
Email: psthomas@mdanderson.org

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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