Pharmacodynamic Study of Estrogen Suppression Threshold-Directed Therapy (ESTDT) of Anastrozole as Adjuvant Therapy for Early Stage Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 161
- 试验地点
- 3
- 主要终点
- Percentage of Participants With Adequate Estrogen Suppression After 8 Weeks of Adjuvant Anastrozole 10 mg Daily
研究概览
简要总结
This phase II trial studies how well anastrozole and letrozole after surgery work in treating patients with stage I-III breast cancer. Drugs, such as anastrozole and letrozole, may stop the growth of tumor cells by decreasing the amount of estrogen made by the body. Giving anastrozole and letrozole after surgery may prevent breast cancer from coming back (recurrence).
详细描述
PRIMARY OBJECTIVE:
I. To estimate the proportion of women who have adequate estrone (E1) and estradiol (E2) suppression after 8-10 weeks of adjuvant anastrozole 10 mg once daily (ANA10) having had inadequate E1 and E2 suppression after 8-10 weeks of standard dose anastrozole 1 mg once daily (ANA1).
SECONDARY OBJECTIVES:
I. To estimate the proportion of women with elevated E1 and E2 levels after 8-10 weeks of adjuvant ANA1.
II. To estimate the proportion of women with elevated E1 and E2 levels after 8-10 weeks of adjuvant ANA1 whose E1 and E2 levels remain elevated after 8-10 weeks of adjuvant ANA10.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •REGISTRATION-INCLUSION CRITERIA
- •Disease characteristics:
- •Histological confirmation of invasive breast carcinoma
- •Stage I-III breast cancer
- •Estrogen receptor (ER) positive disease according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as ER >= 1% positive nuclear staining
- •Completion of all planned cancer treatments prior to registration:
- •Surgical resection of breast and nodal surgery; (NOTE: Reconstructive surgery does not have to be completed)
- •Adjuvant radiation therapy, if needed
- •Neoadjuvant and/or adjuvant chemotherapy, if needed
- •Post-menopausal defined as
- •Age >= 60 and amenorrhea > 12 consecutive months OR
- •Previous bilateral oophorectomy OR
- •Age < 60 and amenorrhea > 12 consecutive months and documented follicle stimulating hormone (FSH) level within post-menopausal range according to institutional standard
- •NOTE: Patients who did not meet these criteria at time of diagnosis and received pre-operative (neoadjuvant) or post-operative (adjuvant) chemotherapy will not be allowed to participate
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- •Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to registration)
- •Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 14 days prior to registration)
- •Platelet count >= 70,000/mm^3 (obtained =< 14 days prior to registration)
- •Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to registration)
- •Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (obtained =< 14 days prior to registration)
- •Ability to swallow oral medication
- •Provide written informed consent
- •Willingness to provide mandatory blood specimens for correlative research
- •Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
- •RE-REGISTRATION-INCLUSION CRITERIA
- •Confirmation that baseline blood sample was drawn and submitted
- •Blood estrogen levels after cycle 1 anastrozole (ANA1) must meet the following criteria:
- •E1 >= 1.3 pg/ml, AND
- •E2 >= 0.5 pg/ml
排除标准
- •REGISTRATION-EXCLUSION CRITERIA
- •Pre-menopausal women receiving ovarian function suppression (goserelin, leuprolide, etc.)
- •Stage IV (metastatic) breast cancer
- •HER2 positive breast cancer as defined by
- •HER2 immunohistochemistry (IHC) >= 3+
- •HER2/CEP17 >= 2.0
- •HER2/CEP17 < 2.0 and average HER2 copy number of >= 6.0 signals/cell
- •Prior endocrine therapy for this breast cancer. Exceptions:
- •Pre-operative aromatase therapy (anastrozole, letrozole, or exemestane) and last treatment was >= 4 weeks prior to registration OR
- •Pre-operative tamoxifen therapy and last treatment was >= 12 weeks prior to registration
- •Currently receiving any of the following cancer-directed therapies:
- •Radiation therapy
- •Systemic therapy such as chemotherapy (standard or investigational)
- •Bisphosphonate therapy started < 4 weeks prior to registration
- •NOTE: If patient is currently on bisphosphonate therapy she must be on stable dose for >= 4 weeks prior to registration. Patients not currently taking bisphosphonates will be allowed to start bisphosphonate therapy after completion of anastrozole (1 mg and 10 mg daily [if given]). Information regarding bisphosphonate therapy will be collected
- •Current use of systemic or topical exogenous estrogen or progesterone (menopausal hormone replacement therapy [HRT])
- •Prior ovarian function suppression (leuprolide, goserelin, etc.)
- •Inability to provide informed consent
- •History of contralateral ductal carcinoma in situ (DCIS) or invasive breast cancer
- •NOTE: Exception allowed if
- •Patient did not receive adjuvant endocrine therapy OR
- •Patient received adjuvant endocrine therapy but has been off treatment for at least 6 months prior to registration
- •Concurrent active malignancy or history of malignancy =< 3 years prior to registration
- •NOTE: Exceptions allowed for successfully treated cervical carcinoma in situ, lobular carcinoma in situ of the breast, papillary thyroid cancer, or non-melanoma skin cancer
- •Prior prevention therapy with an aromatase inhibitor or a selective estrogen receptor modulator (SERM). Exception: Therapy with a SERM (tamoxifen or raloxifene) is allowed if patient has been off treatment for >= 6 months prior to registration
研究组 & 干预措施
Treatment (anastrozole, letrozole)
Patients receive anastrozole PO QD for 56-70 days (8-10 weeks). Patients with E1 >= 1.3 pg/ml and E2 >= 0.5 pg/ml continue to receive anastrozole PO QD for another 56-70 days (8-10 weeks). Patients then receive letrozole PO QD for 8-10 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Anastrozole (Drug)
Treatment (anastrozole, letrozole)
Patients receive anastrozole PO QD for 56-70 days (8-10 weeks). Patients with E1 >= 1.3 pg/ml and E2 >= 0.5 pg/ml continue to receive anastrozole PO QD for another 56-70 days (8-10 weeks). Patients then receive letrozole PO QD for 8-10 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Letrozole (Drug)
结局指标
主要结局
Percentage of Participants With Adequate Estrogen Suppression After 8 Weeks of Adjuvant Anastrozole 10 mg Daily
时间窗: 24 weeks
Percentage of women who have adequate E1 and E2 suppression (E1 \< 1.3 pg/ml and/or E2 \< 0.5) after 8-10 weeks of adjuvant anastrozole 10 mg daily having had inadequate E1 and E2 (E1 \>= 1.3 pg/ml and E2 \>= 0.5) after 8-10 weeks of adjuvant anastrozole 1 mg daily.
次要结局
- Number of Participants Experiencing a Grade 3 or Greater Adverse Event(24 weeks)
- Percent Change in Estrone (E1) and Estradiol (E2) Concentrations(24 weeks)