A Phase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of Participants With Incidence of Adverse Events (Dose Limiting Toxicities)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: 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.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Number of Participants With Incidence of Adverse Events (Dose Limiting Toxicities)
时间窗: 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.
次要结局
- 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)