Imaging Early Response of ER+, HER2- Breast Cancer to Aromatase Inhibitor (AI) +/- Ovarian Suppression (OS) Therapy With [18F]Fluorothymidine (FLT) PET
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Percent Change in Net Influx Constant (Ki) by FLT PET
研究概览
简要总结
This clinical trial studies fluorine F 18 fluorothymidine (FLT) positron emission tomography (PET) in measuring treatment response in patients with newly diagnosed estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage I-III breast cancer. Comparing results of diagnostic procedures done before and during hormone therapy may help doctors predict a patient's response to treatment and help plan the best treatment.
详细描述
PRIMARY OBJECTIVES:
I. Measure the effect of a short course of endocrine therapy on primary breast cancer metabolism and proliferation by measuring changes in serial FLT PET measures pre and post a short course of endocrine therapy.
SECONDARY OBJECTIVES:
I. Compare changes in imaging measures to tissue measures of response, in particular antigen identified by proliferation-related Ki-67 antigen (Ki-67), in the pre-therapy biopsy versus the post-therapy surgical specimen.
II. Correlate imaging measures to measures of gene expression from pre and post therapy assays to determine if there are molecular changes associated with early response to therapy.
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
- •A new diagnosis of invasive breast cancer > 1.0 cm in size, ER+ clinical stage I-III
- •Patient must have surgical resection followed by systemic adjuvant therapy with an aromatase inhibitor (AIs) as part of planned treatment; any approved AI at standard clinical dosing may be used; in pre-menopausal patients, ovarian suppression with a gonadotropin-releasing hormone (GnRH) agonist will be started prior to initiation of the AI on a separate clinical trial in parallel with the imaging study
- •Have tissue block available from core biopsy for correlative biomarkers and genomic assay
- •Have menopausal status determined prior to study enrollment; for study purposes, postmenopausal is defined as
- •A prior documented bilateral oophorectomy, or
- •A history of at least 12 months without spontaneous menstrual bleeding, or
- •Age 60 or older with a prior hysterectomy without oophorectomy, or
- •Age less than 60 with a prior hysterectomy without oophorectomy (or in whom the status of the ovaries is unknown) with a documented follicle-stimulating hormone (FSH) level demonstrating confirmatory elevation in the postmenopausal range for the lab
- •Negative pregnancy test within 7 days of baseline positron emission tomography (PET) scan for pre-menopausal patients
- •Tumor HER2/neu expression must be determined (as part of standard clinical care) prior to study enrollment; HER2 may be tested by any Food and Drug Administration (FDA) approved HER2 testing method; if determination is intermediate by immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) or another alternate HER2 test must be performed
- •Be a candidate for [18F]FLT PET imaging
- •Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific screening procedures
- •Be willing and able to comply with scheduled visits and other trial procedures
排除标准
- •Current use of aromatase inhibitor as prevention or treatment for breast cancer
- •Life expectancy of less than two months
- •HER2/neu positive by IHC and/or another FDA approved HER2 testing method
- •Inability to tolerate scanning (e.g. - claustrophobia, severe pain)
- •Weight exceeding capacity of imaging table
研究组 & 干预措施
Diagnostic (FLT PET)
Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment.
干预措施: Fluorothymidine F-18 (Drug)
Diagnostic (FLT PET)
Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment.
干预措施: Positron Emission Tomography (Procedure)
Diagnostic (FLT PET)
Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment.
干预措施: Laboratory Biomarker Analysis (Other)
Diagnostic (FLT PET)
Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment.
干预措施: Run-in (short pre-surgery course) of endocrine-targeted therapy (Drug)
结局指标
主要结局
Percent Change in Net Influx Constant (Ki) by FLT PET
时间窗: Baseline to up to 6 weeks
Percent change between pre-treatment (baseline) and post-therapy PET measurements in breast tumors will be computed. Association between Ki-67 and Ki by FLT (KFLT) decline will be analyzed using the mid-P adjustment to Fisher's exact test to evaluate the potential clinical utility of change in FLT as a biomarker for early response, using Ki-67 as the standard for early response.
Percent Change in SUV by FLT PET
时间窗: Baseline to up to 6 weeks
Percent change between pre-treatment (baseline) and post-therapy measurements of FLT standardized uptake value (SUV) in breast tumors will be computed.
Percentage of Ki-67 Positive Tumor Cells in Surgical (Post-therapy) Sample
时间窗: 1 to 6 weeks post-therapy start
Surgically removed breast tumor tissue is stained using immuno-histochemistry techniques to visualize dividing cells expressing the Ki-67 protein, which is a cellular marker for proliferation.
Percentage Change in Ki-67 Positive Cells Between Pre-therapy and Post-therapy Tumor Specimens
时间窗: Baseline to up to 6 weeks
Tumor tissue samples from pre-treatment (baseline) biopsy and post-treatment surgery are stained using immuno-histochemistry techniques to visualize dividing cells expressing the Ki-67 protein, which is a cellular marker for proliferation. The % values of positive cells from the baseline and post-treatment samples are then compared for each individual patient. Association between Ki-67 and KFLT decline will be analyzed to evaluate the potential clinical utility of change in FLT as a biomarker for early response, using Ki-67 as the standard for early response.
次要结局
- Post-treatment Standardized Uptake Values (SUV) by FLT PET(1 to 6 weeks post-therapy start)
- Percentage Change in K1 (Blood Flow Parameter) by FLT PET(Baseline to up to 6 weeks)
- Baseline Ki (Flux Constant) Values by FLT PET(Baseline)
- Baseline FLT Transport (K1) Values by FLT PET(Baseline)
- Baseline Standardized Uptake Values (SUV) by FLT PET(Baseline)
- Post-therapy Ki (Flux Constant) Values by FLT PET(1 to 6 weeks post-therapy start)
- Post-treatment FLT Transport (K1) Values by FLT PET(1 to 6 weeks post-therapy start)
研究者
Hannah Linden
Principal Investigator
University of Washington