Alternative Dosing of Exemestane in Postmenopausal Women With Stage 0-II ER-Positive Breast Cancer: A Randomized Presurgical Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 180
- 试验地点
- 5
- 主要终点
- Percent Change in Time of Circulating Estradiol SPE in Each Arm
研究概览
简要总结
This phase IIb trial studies how well alternative dosing of exemestane before surgery works in treating in postmenopausal patients with stage 0-II estrogen positive breast cancer. Chemoprevention is the use of drugs to keep breast cancer from forming or coming back. The use of exemestane may treat early stage (stage 0-II) breast cancer. Comparing the exemestane standard dose regimen versus two alternative, less frequent dose regimens may decrease undesirable symptoms and have similar efficacy in reducing serum estradiol.
详细描述
We have conducted an international, multicenter, pre-surgical double-blind non-inferiority phase IIb study in which a total of 180 participants have been randomized to receive either exemestane 25 mg/day (Exemestane 25 mg QD) or 25 mg/ three times a week (Exemestane 25 mg TIW) or a single dose of 25 mg/week (Exemestane 25 mg QW) for a minimum of 4 up to 6 weeks. Participants were stratified by center and BMI (<25 kg/m2 vs >25 kg/m2).
Participants were histologically confirmed ER-positive (ER >10%) primary breast cancer patients who were candidates for breast surgery. Postmenopausal women younger than 76 years of age with cT0-2, cN0-1, Mx or women with larger tumors who refuse neo-adjuvant therapy before surgery were eligible. No previous treatment for breast cancer was allowed.
Complete physical exam and safety lab tests have been performed at baseline and at the end of treatment (28+1, 35+1, 42+1 days). Phone contact occurred on day 1 and a week before surgery (+3 days). Participants experiencing persistent adverse events (certainly, probably, and possibly treatment-related) have been monitored 20-30 days after study completion.
Biomarkers: blood samples were collected at baseline and the end of treatment (fasting blood for biomarkers collected prior to randomization and either on the day of surgery or the day before; fasting strongly recommended but not mandated), tissue samples collected from the diagnostic or research biopsy and at the time of surgery.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- — 至 75 Years（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Postmenopausal women (postmenopausal: age >= 60 years, or amenorrhea >= 12 months, or bilateral oophorectomy, or - in women with hysterectomy only - follicle stimulating hormone [FSH] in the menopausal levels as per local institutional guidelines if < 60 years old) with histologically-confirmed estrogen receptor (ER)-positive (>= 10%) primary breast cancer stage cT0-2, cN0-1, Mx; women with larger tumors who refuse chemotherapy (chemo) and/or endocrine neoadjuvant therapy can be eligible
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
- •Leukocytes >= 3,000/microliter
- •Absolute neutrophil count >= 1,500/microliter
- •Platelets >= 100,000/microliter
- •Total bilirubin =< 2 x institutional upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional ULN
- •Serum creatinine =< 1.5 times institutional ULN
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Body mass index (BMI) < 18.5 Kg/m^2
- •Previous treatment for breast cancer including chemotherapy, endocrine therapy and radiotherapy; women with prior ductal breast carcinoma in situ (DCIS) who were treated with surgery only and whose treatment ended >= 2 years prior to enrollment are eligible for the trial
- •Women who are planned to receive neoadjuvant therapy
- •Participants may not be receiving investigational agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to exemestane
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Other co-existing invasive malignancies (with the exclusion of basal cell carcinoma or skin squamous cell carcinoma) diagnosed during the last 2 years before randomization
- •History of severe osteoporosis (T score =< -4 either spine or hip), or presence of vertebral fracture
- •Use of systemic hormone replacement therapy (HRT) in the last 30 days prior to the randomization; the use of non-systemic estrogen (such as vaginal estrogen use) is allowed
- •Use of any chemopreventive agents (selective estrogen receptor modulators [SERM]) in the last 3 months
- •Concomitant use of CYP3A4 inducer medication (rifampicin, phenytoin, carbamazepine, phenobarbital, and St. John's wort)
研究组 & 干预措施
Arm II: Exemestane 25 TIW (exemestane, placebo)
Patients receive exemestane PO QD on days 1, 3, and 5. Patients also receive placebo PO QD on days 2, 4, 6, and 7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Pharmacological Study (Other)
Arm I: Exemestane 25 mg QD
Patients receive exemestane PO QD on days 1-7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Exemestane (Drug)
Arm I: Exemestane 25 mg QD
Patients receive exemestane PO QD on days 1-7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I: Exemestane 25 mg QD
Patients receive exemestane PO QD on days 1-7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Pharmacological Study (Other)
Arm I: Exemestane 25 mg QD
Patients receive exemestane PO QD on days 1-7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Quality-of-Life Assessment (Other)
Arm I: Exemestane 25 mg QD
Patients receive exemestane PO QD on days 1-7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Questionnaire Administration (Other)
Arm I: Exemestane 25 mg QD
Patients receive exemestane PO QD on days 1-7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Therapeutic Conventional Surgery (Procedure)
Arm II: Exemestane 25 TIW (exemestane, placebo)
Patients receive exemestane PO QD on days 1, 3, and 5. Patients also receive placebo PO QD on days 2, 4, 6, and 7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Exemestane (Drug)
Arm II: Exemestane 25 TIW (exemestane, placebo)
Patients receive exemestane PO QD on days 1, 3, and 5. Patients also receive placebo PO QD on days 2, 4, 6, and 7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II: Exemestane 25 TIW (exemestane, placebo)
Patients receive exemestane PO QD on days 1, 3, and 5. Patients also receive placebo PO QD on days 2, 4, 6, and 7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Placebo Administration (Other)
Arm II: Exemestane 25 TIW (exemestane, placebo)
Patients receive exemestane PO QD on days 1, 3, and 5. Patients also receive placebo PO QD on days 2, 4, 6, and 7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Quality-of-Life Assessment (Other)
Arm II: Exemestane 25 TIW (exemestane, placebo)
Patients receive exemestane PO QD on days 1, 3, and 5. Patients also receive placebo PO QD on days 2, 4, 6, and 7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Questionnaire Administration (Other)
Arm II: Exemestane 25 TIW (exemestane, placebo)
Patients receive exemestane PO QD on days 1, 3, and 5. Patients also receive placebo PO QD on days 2, 4, 6, and 7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Therapeutic Conventional Surgery (Procedure)
Arm III: Exemestane 25 mg QW (exemestane, placebo)
Patients receive exemestane PO QD on day 1 and placebo PO QD on days 2-7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Exemestane (Drug)
Arm III: Exemestane 25 mg QW (exemestane, placebo)
Patients receive exemestane PO QD on day 1 and placebo PO QD on days 2-7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Laboratory Biomarker Analysis (Other)
Arm III: Exemestane 25 mg QW (exemestane, placebo)
Patients receive exemestane PO QD on day 1 and placebo PO QD on days 2-7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Pharmacological Study (Other)
Arm III: Exemestane 25 mg QW (exemestane, placebo)
Patients receive exemestane PO QD on day 1 and placebo PO QD on days 2-7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Placebo Administration (Other)
Arm III: Exemestane 25 mg QW (exemestane, placebo)
Patients receive exemestane PO QD on day 1 and placebo PO QD on days 2-7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Quality-of-Life Assessment (Other)
Arm III: Exemestane 25 mg QW (exemestane, placebo)
Patients receive exemestane PO QD on day 1 and placebo PO QD on days 2-7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Questionnaire Administration (Other)
Arm III: Exemestane 25 mg QW (exemestane, placebo)
Patients receive exemestane PO QD on day 1 and placebo PO QD on days 2-7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.
干预措施: Therapeutic Conventional Surgery (Procedure)
结局指标
主要结局
Percent Change in Time of Circulating Estradiol SPE in Each Arm
时间窗: baseline and 4-6 weeks
LS means of percent change
次要结局
- Exemestane Blood Concentration at Surgery(at surgery)
- Percent Change of Circulating Estrone SPE(baseline and 4-6 weeks)
- Percent Change of Circulating SHBG(baseline and 4-6 weeks)
- Percent Change of Circulating Testosterone(baseline and 4-6 weeks)
- Percent Change of Circulating LDL Cholesterol(baseline and 4-6 weeks)
- Percent Change of Serum Glucose(baseline and 4-6 weeks)
- 17 OH Exemestane Tissue Concentration at Surgery(4-6 weeks)
- Percent Change in Time of Circulating Estradiol LLE in Each Arm(baseline and 4-6 weeks)
- Percent Change of Circulating Estrone Sulfate(baseline and 4-6 weeks)
- Percent Change of Circulating Androstenedione(baseline and 4-6 weeks)
- Percent Change of Circulating Total Cholesterol(baseline and 4-6 weeks)
- Percent Change of Circulating Insulin(baseline and 4-6 weeks)
- Change of PgR Expression (Cancer Tissue), Central Review(4-6 weeks)
- Change of Ki67% Expression (Adjacent Non Cancer Tissue), Central Review(4-6 weeks)
- 17-OH Exemestane Blood Concentration at Surgery(at surgery)
- Percent Change of Circulating Testosterone CLIA(baseline and 4-6 weeks)
- Percent Change of Circulating Total Estrone(baseline and 4-6 weeks)
- Percent Change of Circulating Leptin(baseline and 4-6 weeks)
- Estradiol Tissue Concentration at Surgery(4-6 weeks)
- Testosterone Tissue Concentration at Surgery(4-6 weeks)
- Percent Change of Circulating Estrone LLE(baseline and 4-6 weeks)
- Percent Change of Circulating HDL Cholesterol(baseline and 4-6 weeks)
- Percent Change of Circulating Triglycerides(baseline and 4-6 weeks)
- Estrone Tissue Concentration at Surgery(4-6 weeks)
- Androstenedione Tissue Concentration at Surgery(4-6 weeks)
- Percent Change of HOMA IR(baseline and 4-6 weeks)
- Percent Change of Circulating Adiponectin(baseline and 4-6 weeks)
- Change of ER Expression (Cancer Tissue), Central Review(4-6 weeks)
- Change of Ki67% Expression (Cancer Tissue), Central Review(4-6 weeks)
- Exemestane Tissue Concentration at Surgery(4-6 weeks)
- Change in MenQoL Questionnaire Score(baseline and 4-6 weeks)