Randomized Placebo-controlled Phase III Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 500
- 试验地点
- 14
- 主要终点
- Number of invasive breast cancer events and DCIS
研究概览
简要总结
The aim of the study is to evaluate whether tamoxifen at a low dose of 5mg/d reduces in the long term the incidence of invasive breast cancer and ductal carcinoma in situ, DCIS (DIN 1c, 2, 3) of the breast, in woman operated for lobular intraepithelial neoplasia (LIN1, 2 and 3) or ER-positive ductal intraepithelial neoplasia (DIN 1b, DIN2, DIN3, 1a excluded) of the breast.
To improve the risk-benefit ratio, the use of lower doses of the drug has been proposed.
Biomarker trials revealed that 5 mg/d was noninferior to 20 mg/d in inhibiting proliferation of breast cancer and normal endometrial tissue.
By contrast, the risk of endometrial cancer si dose-dependent, and the dose reduction can lead a substantial decrease. Morover a dose of 5 mg/day is associated with an overall decrease of the estrogenic activity of tamoxifen on insulin like growth factor (IGF-I), sex hormone-binding globulin (SHBG) and antithrombin-III, with a decrease of venous thromboembolic events. Moreover, tamoxifen exhibits a high tissue distribution, so that a dose of 5 mg/day attains at the breast tissue level a concentration 10 times higher than that needed to inhibit cell growth in vitro.
A prospective cohort study also showed that 10 mg on alternate days halves recurrence of DCIS in postmenopausal women.
It has been shown that the treatment of dysplasia or pre-cancer drives the reduction of the invasive neoplasms onset. This is a chemoprevention trial designed to validatate the low-dose Tamoxifen in women with diseases at high evolutionary risk. The demonstration of efficacy and safety of such a treatment for the prevention of the invasive breast cancer would lead improvements in term of survival and quality of life for the patients at increased risk.
详细描述
Italian, multicenter, phase III trial: controlled, parallel group comparision, randomized (1:1) duble blind, tamoxifen 5 mg/d versus placebo administered for 3 years. A total of 500 women 75 years of age or younger with newly diagnosed non-invasive breast cancer have been included in the study. The long-term study implies a minimum 10 year follow up after treatment completion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women of age ≥ 18 and < 75 years
- •Women operated on for lobular (LIN 2 and 3) or ER positive or unknown ductal DCIS, i.e DIN 1-3, but DIN 1a excluded) intraepithelial neoplasia in the 5 years (60 months) prior the inclusion in the study. Both incident (diagnosis < 12 months) and prevalent cases diagnosis ≥12, and < 60 months) will be included, including recurrent cases
- •ECOG Performance status ≤ 1
- •Written informed consent
排除标准
- •Any type of malignancy, with the exclusion of non-melanoma skin cancer
- •Proliferative disorders of the endometrium such as atypical hyperplasia, endometriosis, unresected polyps, symptomatic myoma
- •Liver, kidney and heart function impairment grade ≥ 2 (CTCAE criteria v.3.0)
- •Any type of retinal disorders, severe cataract and glaucoma
- •Presence of significant risk factors for venous events, including immobilization after trauma within the last 3 months for longer than 2 weeks, deep venous thrombophlebitis or other significant venous thrombotic event,VTE (pulmonary embolism, stroke, etc.)
- •Use of tamoxifen, raloxifene or other selective estrogen receptor modulator (SERMs)
- •Use of anastrozole and other aromatase inhibitors (AI) in the last 12 months for ≥ 6 months
- •Dicoumarol anticoagulant therapy in progress
- •Active infections
- •Severe psychiatric disorders or inability to comply to the protocol procedures
- •Geographic inaccessibility or difficulties in ensuring adequate compliance
- •Women who are pregnant or breastfeeding
- •Any other factor which, at the discretion of the investigator, may controindicate the use of tamoxifen
研究组 & 干预措施
Tamoxifen
tamoxifen at daily dose of 5 mg for a total treatment time of 3 years
干预措施: Tamoxifen (Drug)
placebo
placebo at daily dose of 5 mg for a total treatment time of 3 years
干预措施: placebo (Drug)
结局指标
主要结局
Number of invasive breast cancer events and DCIS
时间窗: 20 years
Number of neoplastic events, i.e., invasive breast cancer or ductal carcinoma in situ of the breast from the start of treatment up to at least 16 years from treatment initiation.
次要结局
- Number of other non-invasive breast events(20 years)
- Metabolites of tamoxifen and hormone blood level (in a subgroup of women)(20 years)
- CYP2D6 polymorphisms analysis(20 years)
研究者
Andrea DeCensi
Medical Oncology Director
Ente Ospedaliero Ospedali Galliera