Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion: a Randomized Phase II Biomarker Trial in Subjects at Increased Risk
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 110
- 试验地点
- 7
- 主要终点
- Post intervention levels of circulating binding globulin
研究概览
简要总结
Circulating levels of Sex Hormone Binding Globulin (SHBG) are significantly associated with a decreased risk of breast cancer.
The main aim of this clinical trial is to verify whether Low Dose Tamoxifen (LDT) increases circulating levels of SHBG more than lifestyle intervention (LI) with or without intermittent caloric restriction (ICR) after 6 months in women at increased risk of breast cancer (i.e., healthy participants carriers of a germline pathogenic/likely pathogenetic variant in at least one of the following genes: BRCA1, BRCA2, PALB2, ATM, CHEK2, CDH1, RAD51C or RAD51D, or with > 5% breast cancer risk at 10 years, using the Tyrer Cuzick or the Breast Cancer Surveillance Consortium Risk models or with a recently resected intraepithelial neoplasia of the breast (IEN).
The secondary aims are:
- to verify whether ICR significantly modulates primary and secondary endpoints such as Homeostasis Model Assessment (HOMA) index, immune and inflammatory markers, lipid profile, Adiponectin/Leptin (A/L) ratio, quality of life (QoL), Body mass index (BMI), fat body composition, safety and toxicity;
- to verify whether LDT significantly modulates secondary endpoints, such as HOMA-index, immune and inflammatory markers, lipid profile, A/L ratio, QoL, BMI, fat body composition, safety and toxicity;
- to investigate differences in microbiome composition by arms and the effect of changes in microbiome on QoL taking into account circulating biomarkers, cytokines, immune modulators, and inflammatory proteins in serum;
- to investigate MD (Mammographic Breast Density) changes by LDT vs. LI, with or without ICR. This aim will be performed in a subgroup of participants (not all the participants will undergo mammography due to younger age).
详细描述
Italian, multicenter, phase II, biomarker trial. A total of 110 women aged 18-70 years will be randomly assigned (1:1:1:1) to one of the four intervention arms Arm 1: Low dose Tamoxifen (LDT) i.e. 10 mg every other day; Arm 2: Low dose Tamoxifen (LDT) + Intermittent Caloric Restriction (ICR); Arm 3: Lifestyle intervention (LI) using a step counter; Arm 4: Lifestyle intervention (LI) using a step counter + Intermittent Caloric Restriction (ICR).
Participants will be stratified by center and by disease status (high risk vs. previous IEN) and intervention will last six months for all arms.
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
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Women between 18 and 70 years old;
- •Healthy participants carriers of a germline pathogenic/likely pathogenetic variant in at least one of the following genes BRCA1, BRCA2, PALB2, ATM, CHEK2, CDH1, RAD51C or RAD51D, or
- •> 5% breast cancer risk at 10 years, using the Tyrer Cuzick or the Breast Cancer Surveillance Consortium Risk models, or
- •with previous diagnosis of intraepithelial neoplasia (surgery for ADH, LCIS, ER positive DCIS) within the last 3 years;
- •Ability to understand and the willingness to sign a written informed consent document;
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1;
- •5a. For high-risk strata: A negative mammogram or any radiological image based on age and center protocol screening within 6 months before baseline visit;
- •5b. For IEN Strata: A negative mammogram within 12 months before baseline visit;
- •6. A negative transvaginal ultrasound within 6 months before baseline visit.
排除标准
- •Diagnosis of ER-negative (<10%) DCIS, or history of invasive breast cancer;
- •Previous treatment with SERMs or any other hormonal treatment for breast neoplasms;
- •BMI < 18.5 Kg/m2 and/or Malnutrition Universal Screening Tool (MUST) score ≥2 and/or any current or past eating disorders;
- •Any diagnosis of invasive neoplasia, except non-melanoma skin cancer, in the previous 5 years;
- •Any tamoxifen contraindications (abnormal liver function, previous ischemic heart disease, endometrial disorder, previous deep venous thrombosis, history of pulmonary embolus, current or suspected glaucoma, retinopathy and cataract);
- •Current use of warfarin or other anticoagulant drugs
- •Bilateral mastectomy;
- •Pregnancy or desire to become pregnant in the subsequent 9 months after treatment cessation;
- •Diabetes or any other clinical condition that at the investigator's discretion contraindicates the proposed intervention.
- •No hormonal contraception is allowed during study intervention. Non-hormonal methods will be advised for women of childbearing potential (WOCBP)
研究组 & 干预措施
Low dose tamoxifen
Tamoxifen 10 mg (1 tablet) every other day for 6 months.
干预措施: Tamoxifen 10 mg Tablet (Drug)
Low dose tamoxifen + Intermittent Caloric Restriction
Tamoxifen 10 mg (1 tablet) every other day for 6 months + 5:2 diet (5 days/week at regular energy intake+2 days a week at an average 75% energy deficit)
干预措施: Tamoxifen 10 mg Tablet (Drug)
Low dose tamoxifen + Intermittent Caloric Restriction
Tamoxifen 10 mg (1 tablet) every other day for 6 months + 5:2 diet (5 days/week at regular energy intake+2 days a week at an average 75% energy deficit)
干预措施: Intermittent caloric restriction (Other)
Lifestyle intervention
Step counter device
干预措施: Step counter Device (Behavioral)
Lifestyle Intervention + Intermittent Caloric Restriction
Step counter device + 5:2 diet (5 days/week at regular energy intake+2 days a week at an average 75% energy deficit)
干预措施: Intermittent caloric restriction (Other)
Lifestyle Intervention + Intermittent Caloric Restriction
Step counter device + 5:2 diet (5 days/week at regular energy intake+2 days a week at an average 75% energy deficit)
干预措施: Step counter Device (Behavioral)
结局指标
主要结局
Post intervention levels of circulating binding globulin
时间窗: Through study completion, an average of 6 months
Sex hormone binding globulin level after 6 months of intervention
次要结局
未报告次要终点