An Exploratory, Open-Label Phase I Pharmacodynamic Study of COX-2 Inhibition With Celecoxib (Celebrex) and Aromatase Activity in Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Change in aromatase activity levels
研究概览
简要总结
This randomized phase I trial is studying the side effects of celecoxib in treating postmenopausal women with invasive breast cancer who are scheduled to undergo surgery at Memorial Sloan-Kettering Cancer Center. Celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.
详细描述
PRIMARY OBJECTIVES:
I. Determine whether celecoxib suppresses aromatase activity in postmenopausal women with invasive breast cancer planning to undergo surgery.
SECONDARY OBJECTIVES:
I. Correlate celecoxib-mediated inhibition of aromatase activity with levels of cyclooxygenase (COX)-2 and HER-2/neu and estrogen receptor status in these patients.
II. Determine the effect of this drug on histology, Ki67, RNA expression profile by microarray analysis, PI3-K, AKT and ERK1/2 MAP kinase activities, and PGE_2 levels in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Histologically confirmed invasive breast carcinoma
- •Tumor at least 1 cm by radiologic estimate or physical exam
- •No disease limited to ductal carcinoma in situ only
- •Planning to undergo surgery at Memorial Sloan-Kettering Cancer Center
- •Hormone receptor status:
- •Not specified
- •Postmenopausal as defined by at least 1 of the following:
- •No menstrual period within the past 12 months
- •Prior bilateral oophorectomy
- •No known liver disease
- •No renal insufficiency
- •No congestive heart failure
- •No coronary artery disease
- •No history of documented peptic ulcer disease
- •No gastritis
- •No medical condition that would preclude definitive surgery
- •No allergy to NSAIDs or sulfa-containing drugs
- •No connective tissue diseases, including any of the following:
- •Systemic lupus erythematosus
- •Reynaud's disease
- •Scleroderma
- •More than 3 months since prior chemotherapy
- •More than 2 weeks since prior hormone replacement therapy
- •More than 2 weeks since prior tamoxifen
- •More than 2 weeks since prior aromatase inhibitors
- •More than 2 weeks since prior raloxifene
- •More than 2 weeks since prior steroids
- •More than 1 week since prior nonsteroidal anti-inflammatory drugs (NSAIDs)
- •More than 1 week since prior cyclooxygenase (COX)-2 inhibitors
- •No concurrent warfarin
- •No concurrent thiazide or loop diuretics
- •No concurrent COX-2 inhibitors
- •No concurrent NSAIDs
排除标准
- 未提供
研究组 & 干预措施
Arm I (celecoxib)
Patients receive oral celecoxib twice daily for 1-3 weeks (according to the duration between biopsy and surgery) in the absence of unacceptable toxicity.
干预措施: celecoxib (Drug)
Arm I (celecoxib)
Patients receive oral celecoxib twice daily for 1-3 weeks (according to the duration between biopsy and surgery) in the absence of unacceptable toxicity.
干预措施: therapeutic conventional surgery (Procedure)
Arm I (celecoxib)
Patients receive oral celecoxib twice daily for 1-3 weeks (according to the duration between biopsy and surgery) in the absence of unacceptable toxicity.
干预措施: pharmacological study (Other)
Arm I (celecoxib)
Patients receive oral celecoxib twice daily for 1-3 weeks (according to the duration between biopsy and surgery) in the absence of unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Arm II (high-dose celecoxib)
Patients receive a higher dose of oral celecoxib as in arm I.
干预措施: celecoxib (Drug)
Arm II (high-dose celecoxib)
Patients receive a higher dose of oral celecoxib as in arm I.
干预措施: therapeutic conventional surgery (Procedure)
Arm II (high-dose celecoxib)
Patients receive a higher dose of oral celecoxib as in arm I.
干预措施: pharmacological study (Other)
Arm II (high-dose celecoxib)
Patients receive a higher dose of oral celecoxib as in arm I.
干预措施: laboratory biomarker analysis (Other)
Arm III (surgery)
Patients do not receive treatment. All patients undergo surgery.
干预措施: therapeutic conventional surgery (Procedure)
Arm III (surgery)
Patients do not receive treatment. All patients undergo surgery.
干预措施: pharmacological study (Other)
Arm III (surgery)
Patients do not receive treatment. All patients undergo surgery.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Change in aromatase activity levels
时间窗: From baseline to post-surgery
次要结局
- Change in cell proliferation via a marker Ki67 between treatment arms by immunohistochemistry(From baseline to post-treatment)
- Effect of treatment vs. no treatment on gene expression (mRNA) profile by microarray, kinase activities (PI3, AKT and ERK1/2 MAP kinases) and PGE2 levels(At post-treatment/surgery)
- Correlation between aromatase activity and levels of COX 2 protein, HER 2/neu and ER status in surgical specimens(At post-treatment/surgery)