Patient-related Predictors of Estrogen Suppression in Postmenopausal Women Using Adjuvant Letrozole
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 121
- 试验地点
- 3
- 主要终点
- Part A Correlation of Day 29 Estrone With Vitamin D
研究概览
简要总结
The purpose of this study is to examine how key patient factors, including body size affect how well letrozole suppresses circulating estrogen levels.
This study has two components: (1) Part A - an observational phase to evaluate the impact of vitamin D and obesity on estrogen suppression in post-menopausal women already receiving letrozole treatment, and (2) Part B - an interventional phase for women with body mass index (BMI) > 25 kg/m2 to assess the effect of double AI dose on estrogen levels.
If BMI or other patient factors reduce the effectiveness of letrozole, modifications to treatment recommendations and studies to test higher dosing of letrozole may be needed to maximize the benefit of this treatment and minimize the risk of the breast cancer coming back.
详细描述
The available evidence suggests that circulating estradiol levels play a critical role in determining effectiveness of aromatase inhibitor therapy, and that maximal suppression of aromatase activity and estrogen production is essential for optimal disease control. Host factors such as high 25-Hydroxy Vitamin D (25-OH D) levels and obesity, which might increase residual estrogen levels, could adversely impact outcome and lead to an increased risk of recurrence or death. The primary objective of Part A (which includes women regardless of BMI) is to directly evaluate the relationship between (i) 25-OH D levels and serum estrogen levels and (ii) BMI and serum estrogen levels in a cohort of postmenopausal women on standard dose letrozole therapy (2.5 mg/day). Part B (which includes only women with BMI > 25 kg/m2) will determine whether an increased dose of letrozole (5 mg/day), which had no dose limiting side effects in a Phase I study improves suppression of estrogen in overweight/obese women.
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
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Postmenopausal female patients
- •histological confirmed diagnosis of estrogen receptor and/or progesterone receptor positive breast cancer (Stage I-III) who have completed local therapy
- •Currently prescribed and taking letrozole 2.5 mg daily for a minimum of 3 months
- •Willing to provide written informed consent to participate
- •for the experimental arm: all of the above and body mass index (BMI) > 25 kg/m2
排除标准
- •Known abnormal liver or renal function defined by:
- •Serum Creatinine > 1.25 times institutional upper limit of normal (ULN) or Calculated Creatinine Clearance < 40 mL/min
- •Serum Bilirubin, Aspartate transaminase (AST) or alanine transaminase (ALT) > 1.5 times ULN
- •Presence of persistent local or known metastatic cancer
研究组 & 干预措施
Post-menopausal Women Using Adjuvant Letrozole
Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants
干预措施: Letrozole (Drug)
结局指标
主要结局
Part A Correlation of Day 29 Estrone With Vitamin D
时间窗: Day 29
Determine if estrone levels vary with Vitamin D levels levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estrone and log-transformed Vitamin D level
Part A Correlation of Day 29 Estradiol With Vitamin D
时间窗: Day 29
Determine if estradiol levels vary with Vitamin D levels levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed Vitamin D level
Part B Change in Estradiol Level After Double Dose of Letrozole
时间窗: Day 29 to Day 58
In overweight/obese patients enrolled in part B, determine if blood levels of estradiol levels changed from before to after the double dose of letrozole
Part A Correlation of Day 29 Estradiol With BMI
时间窗: Day 29
Determine if estradiol levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed BMI
Part A Correlation of Day 29 Estrone With BMI
时间窗: Day 29
Determine if estrone levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estrone and log-transformed BMI
次要结局
- Endocrine Symptoms During Part A of Study(baseline, day 29 (end of part A))
- Endocrine Symptoms During Part B of the Study(day 29 (end of part A) and day 58 (end of part B))
- Plasma Letrozole(Day 29 and day 58)