Pilot Study of Daily Exemestane in Women With Complex Atypical Hyperplasia of the Endometrium/Endometrial Intraepithelial Neoplasia or Low Grade Endometrial Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 3
- 主要终点
- Change in Tumor Proliferation
研究概览
简要总结
This pilot phase IIa trial studies how well exemestane works in treating patients with complex atypical hyperplasia of the endometrium/endometrial intraepithelial neoplasia or low grade endometrial cancer. Exemestane may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVE:
I. To determine if there is a decrease in proliferation index, measured by Ki-67 expression, in complex atypical hyperplasia (CAH)/endometrial intraepithelial neoplasia (EIN) or low grade (grade 1 and grade 2) endometrial cancer cells from baseline to post-exemestane treatment.
SECONDARY OBJECTIVES:
I. Circulating serum estradiol and progesterone. II. Pathological response (regression of CAH/EIN or low grade [grade 1 and grade 2] endometrial carcinoma).
III. Tissue biomarkers. IV. Deoxyribonucleic acid (DNA) mutational analysis through next generation sequencing and methylation status of endometrial tumor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Females with a histologically proven CAH/ EIN or low grade (grade 1 or grade 2) endometrial carcinoma (EC) for which surgery is planned; the pathologic report from the referring facility will be used to determine pathologic eligibility; this report must be within 45 days of their baseline (pre-surgical) clinic visit
- •No prior treatment for CAH/EIN/EC
- •Post-menopausal confirmed with one the following criteria:
- •>= 60 years of age
- •Age 56 to 59 years of age with >= 2 years of amenorrhea
- •Age 56 to 59 years of age with < 2 years of amenorrhea and follicle stimulating hormone (FSH) within institutional post-menopausal range.
- •Age 45 to 55 years of age with FSH within institutional post-menopausal range. The Ki-67 expression changes based on menopausal status and specifically varies based on what phase of the menstrual cycle the sample is collected. Therefore, in order to eliminate this source of variability, only postmenopausal women will be included in this trial. In addition, exemestane is currently approved for use in post-menopausal women only.
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- •Hemoglobin >= 9 g/dL
- •Serum creatinine =< 1.5 x upper limit of normal or calculated creatinine clearance >= 60 mL/min using Cockcroft-Gault equation for patients with creatinine levels > 1.5 x institutional upper limit of normal (ULN)
- •Total bilirubin =< 1.5 x ULN OR direct bilirubin =< 1 x ULN
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
- •White blood cell (WBC) >= 3000/mcl
- •Platelets >= 100,000/mcl
- •Able and willing to take oral medications
- •Ability to understand and the willingness to sign a written informed consent document
- •Body mass index (BMI) > 20
排除标准
- •Participants who had curatively treated invasive malignancies for which all treatments ended within 1 year prior to the study (with the exception of basal cell or squamous cell carcinoma of the skin)
- •Not a surgical candidate or surgery is not scheduled within 43 days from starting the study drug
- •Receiving any other investigational agents
- •Any gastrointestinal condition causing malabsorption or obstruction (e.g. celiac sprue, gastric bypass surgery, strictures, adhesions, history of small bowel resection, blind loop syndrome)
- •Has been on any hormonal treatment (including progestin-containing intrauterine device [IUD]) for CAH/EIN or low grade (grade 1 or grade 2) endometrial carcinoma in last 3 months
- •Use hormone replacement therapy (including systemic or topical estrogen, progesterone, or testosterone based medication) or/and phytoestrogen supplements (i.e. black cohosh) or has been on progestin (including progestin containing IUD), tamoxifen or aromatase inhibitor within the prior 3 months
- •Concomitant use of strong CYP3A4 inducers such as rifampicin, phenytoin, carbamazepine, phenobarbital or St. John's wort as these may significantly reduce the availability of exemestane
- •Known hypersensitivity to exemestane or its excipients
- •Known intercurrent illness or psychiatric illness/social situations that will limit compliance with study requirements
- •Evidence or high suspicion of metastatic disease at enrollment
- •Women with severe bone density issues/osteoporosis (defined as any medical treatment for osteoporosis, and/or a T-score of -2.5 or lower, and/or history of fracture of the hip or spine)
- •Unwilling or unable to undergo research biopsy during the baseline (pre-surgical) clinic visit, or inadequate research biopsy obtained during the baseline (pre-surgical) clinic visit (determined by the gynecologic oncologist at the time of the subject's pelvic exam)
研究组 & 干预措施
Treatment (exemestane)
Patients receive exemestane PO QD over 21-42 days in the absence of disease progression or unaccepted toxicity. Patients undergo standard of care surgery between days 22-43.
干预措施: Exemestane (Drug)
Treatment (exemestane)
Patients receive exemestane PO QD over 21-42 days in the absence of disease progression or unaccepted toxicity. Patients undergo standard of care surgery between days 22-43.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (exemestane)
Patients receive exemestane PO QD over 21-42 days in the absence of disease progression or unaccepted toxicity. Patients undergo standard of care surgery between days 22-43.
干预措施: Pharmacokinetic Study (Other)
Treatment (exemestane)
Patients receive exemestane PO QD over 21-42 days in the absence of disease progression or unaccepted toxicity. Patients undergo standard of care surgery between days 22-43.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Change in Tumor Proliferation
时间窗: Baseline up to 2 months
Will be measured by change in Ki-67 expression. Will evaluate the change from baseline to post-exposure in absolute change in percent Ki-67 using one-sample Student's t-test or Wilcoxon signed-rank test, as appropriate.
次要结局
- Ki-67 Expression With Historic Controls(Up to 2 months)
- Plasma Levels of Exemestane(Up to 2 months)
- Changes in Circulating Serum Estradiol(Baseline up to 2 months)
- Changes in Circulating Serum Progesterone(Baseline up to 2 months)
- Percent of Participants by Pathological Response Class at 2 Months(Up to 2 months)
- Change From Baseline in Percent of Cells Positive for Tissue Markers(Up to 2 months)
- Deoxyribonucleic Acid (DNA) Mutational Analysis(Up to 2 months)
- Protein Markers(Up to 2 months)