Phase IIB Randomized Trial of Oral Tamoxifen vs. Topical 4-hydroxytamoxifen Gel vs. Control in Women With Atypical Hyperplasia, Lobular Carcinoma in Situ, or Increased Breast Cancer Risk
概览
- 阶段
- 2 期
- 干预措施
- Tamoxifen
- 疾病 / 适应症
- Breast Atypical Hyperplasia
- 发起方
- Mayo Clinic
- 入组人数
- 65
- 试验地点
- 3
- 主要终点
- The purpose of this research is to evaluate short-term changes in background breast tissue induced by oral tamoxifen or 4-OHT gel in women with atypical hyperplasia or lobular carcinoma in situ (LCIS).
- 状态
- 终止
- 最后更新
- 3个月前
概览
简要总结
The investigators plan to prospectively study breast tissue changes after a short course of Tamoxifen (Tam).
详细描述
Women with atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS) are at increased risk of breast cancer (BC) (\~1-2 % per year). Over two decades ago, placebo-controlled randomized trials established that oral tamoxifen (20 mg/day) reduces breast cancer risk by 50% in generally defined high risk women, with \~70% reduction in women at high risk specifically due to atypical hyperplasia.\[1\] Years later, the side effects and toxicity of oral tamoxifen at 20 mg/day remain a significant barrier to its uptake and longterm compliance.\[2, 3\] To address the issue of toxicity, two main strategies have been pursued: 1) using a lower dose of oral tamoxifen, and 2) using a topical formulation of tamoxifen to avoid systemic side effects. The investigators will perform a prospective study of women with AH or LCIS who will take a short course of prevention therapy; breast tissue samples will be evaluated pre- and post-therapy to identify and evaluate very early biomarkers of response. The overall goal of the study is to evaluate short-term changes in background breast tissue induced by either low-dose oral tamoxifen or topical 4-OHT gel in women with AH or LCIS.
研究者
入排标准
入选标准
- •Willing to return to enrolling institution for follow-up
- •Willing to complete required testing
- •Ability to complete questionnaire by themselves or with assistance
- •Female (sex that was assigned at birth)
- •Ipsilateral intact breast with histology confirmation of atypical ductal or lobular hyperplasia, or lobular carcinoma in situ (LCIS), within the last 12 months, whether surgically excised or not.; OR neither AH nor LCIS but increased breast cancer risk defined as either:
- •Gail model (Breast Cancer Risk Assessment Tool) 5 year breast cancer risk of \>= 3%, or
- •International Breast Intervention Study model 10 year breast cancer risk of \>= 5%.
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
- •The effects of topical afimoxifene (4-OHT) gel on the developing human fetus at the recommended therapeutic dose are unknown. However, oral tamoxifen is Pregnancy Category D-positive evidence of human fetal risk. For this reason, and because triphenylethylene antiestrogens, including tamoxifen, are known to be teratogenic, women of childbearing potential and their male partners must agree to use at least one effective form of birth control (abstinence is not an allowed method) prior to study entry and for the duration of study participation, and for 2 months following the last dose of study medications (participant can resume oral birth control pills for effective birth control measures after post-treatment biopsy is done). Effective birth control methods during treatment are: copper and Mirena intrauterine device (IUD), diaphragm/cervical cap/shield, spermicide, contraceptive sponge, condoms. Tubal Ligation is an acceptable method of birth control. Women of childbearing potential must have a negative pregnancy test within five days before starting study medications. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.
- •Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the duration of the study.
排除标准
- •Clinically suspicious mass/lesions
- •Breast cancer in the past 5 years.
- •Patients with any history of venous thromboembolic disease, regardless of timeframe (history of varicose veins and superficial phlebitis is allowed).
- •Current pregnancy or lactation.
- •History of other prior breast cancer-specific therapy within the previous 2 years (chemotherapy, anti-HER2 agents, endocrine agents, everolimus, CDK4-6 inhibitors).
- •Cytotoxic chemotherapy for any indication in last 2 years.
- •Prior use of selective estrogen receptor modulator (SERMS) or AIs including tamoxifen, raloxifene, anastrozole, letrozole, or exemestane for prevention or therapy within the past 5 years unless:
- •Use was less than 6 months duration in the past 5 years and not used in the 1 year prior to enrollment, or
- •Use was no greater than 2 months duration in the past 1 year and not used in the 6 months prior to enrollment.
- •Exogenous sex steroid, including oral contraceptive pill use within 1 month prior to pretreatment breast biopsy. Use of vaginally administered estrogens and hormone coated IUD such as Mirena is permitted.
研究组 & 干预措施
Oral Tamoxifen 10 mg/day
Oral Tamoxifen 10 mg/day
干预措施: Tamoxifen
Oral Tamoxifen 10 mg/day
Oral Tamoxifen 10 mg/day
干预措施: Questionnaire Administration
Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day
Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day +oral placebo
干预措施: Topical 4-OHT( 4-hydroxytamoxifen)gel 4 mg/each breast/day
Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day
Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day +oral placebo
干预措施: Questionnaire Administration
Control
Oral and gel placebo
干预措施: Placebo
Control
Oral and gel placebo
干预措施: Questionnaire Administration
结局指标
主要结局
The purpose of this research is to evaluate short-term changes in background breast tissue induced by oral tamoxifen or 4-OHT gel in women with atypical hyperplasia or lobular carcinoma in situ (LCIS).
时间窗: 48 months
Treatment Evaluation/Measurement of Effect