In Vivo Imaging of the Effect of Fulvestrant on the Availability of Estrogen Receptor Binding Sites in Metastatic Breast Tumor Lesions Using FES-PET
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- To evaluate the proportion of patients with an incomplete down-regulation/occupancy of ERs as determined by FES-PET
研究概览
简要总结
The dose of fulvestrant to optimally downregulate estrogen receptors (ER) is currently subject of debate. Effects of fulvestrant on the ERs may be evaluable by molecular imaging using positron emission tomography with the ER-specific FES tracer. In this pilot study we will evaluate the effects of the new dose of fulvestrant (500mg i.m.)on the availability of ER binding sites in 15 metastatic breast cancer patients.
详细描述
The estrogen receptor (ER) is expressed in approximately 70% of the breast carcinomas. In these patients signaling via the ER induces proliferation and cell survival of malignant cells. Fulvestrant can inhibit this signaling route by blocking the receptor and decreasing ER-expression by increasing its turn-over rate.
The historical standard dose of fulvestrant was 250mg every 28 days i.m.; however studies performing serial biopsies showed that ER-downregulation was suboptimal. Recently the standard dose has been set to 500mg i.m. on day 1; 14; 28 and every 28 days thereafter. Although slightly more effective than the 250mg dose, still questions remain with respect to the required dose to establish maximal downregulation of ER-signaling.
Immunohistochemistry only provides static information, i.e. the level of ER-expression. However, dynamic information evaluating the effects of fulvestrant on occupancy of ERs, may also be valuable.
Whole-body imaging of the availability of ER binding sites using FES-PET may prove valuable to evaluate the effects of fulvestrant on the ER non-invasively in individual patients. This potentially allows adjustment of dosing in individual patients to aid therapy efficacy.
In this pilot-study we will evaluate 15 metastatic breast cancer patients. All patients will undergo FES-PET/CT at baseline, FES-PET after 1 month, and FES-PET/CT after three months. Hormone- and fulvestrant levels will be measured in all patients. Whenever possible, tumor biopsies will be performed to correlate to FES-PET results.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a history of histological proven ER-positive primary breast cancer and, whenever available, histological proven ER-positive recurrence.
- •Post-menopausal status (age ≥ 45 years with amenorrhea for > 12 months or prior bilateral ovariectomy
- •Documentation of a negative pregnancy test must be available for women less than 2 years after menopause
- •Progressive disease after 2 lines of hormonal therapy
- •No previous fulvestrant treatment
- •ER-antagonists should be discontinued for 5 weeks prior to FES-PET to prevent false negative FES-PET results. The use of aromatase inhibitors is allowed
- •ECOG performance status 0, 1 or 2
- •Life expectancy > 3 months
- •Creatinine clearance ≥ 30 ml/min
- •Age ≥ 18 years
- •Signed written informed consent
- •Able to comply with the protocol
排除标准
- •Evidence of central nervous system metastases
- •Presence of life-threatening visceral metastases
- •> 3 lines of endocrine therapy for metastatic disease
- •> 2 lines of chemotherapy in metastatic disease
结局指标
主要结局
To evaluate the proportion of patients with an incomplete down-regulation/occupancy of ERs as determined by FES-PET
时间窗: baseline, 1 month and 3 months
FES-uptake will be calculated for all tumor lesions at baseline, after 1 month and after 3 months. Incomplete down-regulation/ occupancy of ERs is defined as 1) an absolute SUV\> 1.5, and 2) a relative decrease in SUV of \<75% during fulvestrant therapy. The proportion of patients that match these criteria will be given for: * 1 month minus baseline * 3 months minus baseline
Visualize and quantify changes in FES uptake in tumor lesions during fulvestrant 500mg therapy
时间窗: baseline; 1 month; 3 months
FES-uptake will be calculated for all tumor lesions at baseline, 1 month and 3 months. Changes between FES-uptake during fulvestrant therapy will be calculated for: * 3 months minus baseline * 3 months minus 1 month * 1 month minus baseline
次要结局
- The feasibility to quantify changes in FES-uptake in liver metastases(baseline, 1 month and 3 months)
- Explorative analysis to correlate several factors (among which tumor burden, ER-expression, fulvestrant levels, estradiol levels, patient weight) to FES uptake will be performed.(baseline, 1 month and 3 months)
- to correlate FES-PET results to patient and tumor response on fulvestrant therapy(baseline, 1 month, 3 months)