NCT04067726进行中（未招募）2 期
Randomized Clinical Trial of RANKL Inhibition With Denosumab on Mammographic Density in Premenopausal Women With Dense Breasts (TRIDENT)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 210
- 试验地点
- 1
- 主要终点
- Change in mammographic breast density between the two arms as measured by volumetric percent density
研究概览
简要总结
Data supporting a role for RANKL signaling in mammographic density and breast cancer development has begun to emerge, but clinical trial data providing definitive evidence that would allow the adoption of RANKL inhibition in primary breast cancer prevention are not yet available. The hypothesis is that RANKL inhibition with denosumab will decrease mammographic density in high-risk premenopausal women with dense breasts. To address this, the investigators have developed this clinical trial to quantify the impact of RANKL inhibition on mammographic density in high-risk premenopausal women with dense breasts and to determine the effect of RANKL inhibition on markers of proliferation and biomarkers of breast cancer risk. Successful demonstration that RANKL inhibition reduces mammographic density could open up additional approaches to primary breast cancer prevention in high-risk premenopausal women, who do not have dominant genetic predisposition.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Premenopausal (when menopausal status is uncertain, the investigators will measure follicle-stimulating hormone and estradiol to ascertain that a partcipant is premenopausal)
- •At least 40 years of age.
- •Dense breasts on routine mammogram (BI-RADS Category C and D)
- •Able to understand and willing to sign an IRB-approved written informed consent document.
排除标准
- •History of breast or any other invasive cancer except for DCIS (ductal carcinoma in situ) who received only lumpectomy, LCIS (lobular carcinoma in situ), atypical hyperplasia, non-melanoma skin cancer, carcinoma in situ of the cervix.
- •Current use of tamoxifen, aromatase inhibitors, or bisphosphonates, or RANKL inhibitors
- •Concurrent participation in another cancer chemoprevention trial (unless no longer receiving the intervention).
- •Pregnant, lactating, or planning to get pregnant while the trial is ongoing.
- •Recent history of invasive dental procedure (e.g. tooth extraction, dental implant, oral surgery).
- •Unhealed and/or planned dental/oral surgery.
- •History of osteonecrosis/osteomyelitis of the jaw.
- •History of osteoporosis or severe osteopenia.
研究组 & 干预措施
Denosumab
Experimental
- Subcutaneous injection of denosumab at a dose of 60 mg at two time points: baseline and 6 months
- Participants will also be instructed to take calcium and vitamin D supplements daily for 12 months between baseline examination and 12-month mammographic breast density examination.
- Mammographic breast density will be assessed at three time points in all participants: baseline, 12 months, and 24 months. A 36-month optional assessment may also occur.
- Biopsies and blood draws will occur for research purposes at baseline and 12 months.
干预措施: Denosumab (Drug)
Denosumab
Experimental
- Subcutaneous injection of denosumab at a dose of 60 mg at two time points: baseline and 6 months
- Participants will also be instructed to take calcium and vitamin D supplements daily for 12 months between baseline examination and 12-month mammographic breast density examination.
- Mammographic breast density will be assessed at three time points in all participants: baseline, 12 months, and 24 months. A 36-month optional assessment may also occur.
- Biopsies and blood draws will occur for research purposes at baseline and 12 months.
干预措施: Calcium (Drug)
Denosumab
Experimental
- Subcutaneous injection of denosumab at a dose of 60 mg at two time points: baseline and 6 months
- Participants will also be instructed to take calcium and vitamin D supplements daily for 12 months between baseline examination and 12-month mammographic breast density examination.
- Mammographic breast density will be assessed at three time points in all participants: baseline, 12 months, and 24 months. A 36-month optional assessment may also occur.
- Biopsies and blood draws will occur for research purposes at baseline and 12 months.
干预措施: Vitamin D3 (Drug)
Denosumab
Experimental
- Subcutaneous injection of denosumab at a dose of 60 mg at two time points: baseline and 6 months
- Participants will also be instructed to take calcium and vitamin D supplements daily for 12 months between baseline examination and 12-month mammographic breast density examination.
- Mammographic breast density will be assessed at three time points in all participants: baseline, 12 months, and 24 months. A 36-month optional assessment may also occur.
- Biopsies and blood draws will occur for research purposes at baseline and 12 months.
干预措施: Core needle biopsy (Procedure)
Denosumab
Experimental
- Subcutaneous injection of denosumab at a dose of 60 mg at two time points: baseline and 6 months
- Participants will also be instructed to take calcium and vitamin D supplements daily for 12 months between baseline examination and 12-month mammographic breast density examination.
- Mammographic breast density will be assessed at three time points in all participants: baseline, 12 months, and 24 months. A 36-month optional assessment may also occur.
- Biopsies and blood draws will occur for research purposes at baseline and 12 months.
干预措施: Blood draw (Procedure)
Placebo
Placebo Comparator
- Subcutaneous injection of the placebo at a dose of 60 mg at two time points: baseline and 6 months
- Participants will also be instructed to take calcium and vitamin D supplements daily for 12 months between baseline examination and 12 month mammographic breast density examination
- Mammographic breast density will be assessed at three time points in all participants: baseline, 12 months, and 24 months. A 36 month optional assessment may also occur.
- Biopsies and blood draws will occur for research purposes at baseline and 12 months.
干预措施: Placebo (Drug)
Placebo
Placebo Comparator
- Subcutaneous injection of the placebo at a dose of 60 mg at two time points: baseline and 6 months
- Participants will also be instructed to take calcium and vitamin D supplements daily for 12 months between baseline examination and 12 month mammographic breast density examination
- Mammographic breast density will be assessed at three time points in all participants: baseline, 12 months, and 24 months. A 36 month optional assessment may also occur.
- Biopsies and blood draws will occur for research purposes at baseline and 12 months.
干预措施: Calcium (Drug)
Placebo
Placebo Comparator
- Subcutaneous injection of the placebo at a dose of 60 mg at two time points: baseline and 6 months
- Participants will also be instructed to take calcium and vitamin D supplements daily for 12 months between baseline examination and 12 month mammographic breast density examination
- Mammographic breast density will be assessed at three time points in all participants: baseline, 12 months, and 24 months. A 36 month optional assessment may also occur.
- Biopsies and blood draws will occur for research purposes at baseline and 12 months.
干预措施: Vitamin D3 (Drug)
Placebo
Placebo Comparator
- Subcutaneous injection of the placebo at a dose of 60 mg at two time points: baseline and 6 months
- Participants will also be instructed to take calcium and vitamin D supplements daily for 12 months between baseline examination and 12 month mammographic breast density examination
- Mammographic breast density will be assessed at three time points in all participants: baseline, 12 months, and 24 months. A 36 month optional assessment may also occur.
- Biopsies and blood draws will occur for research purposes at baseline and 12 months.
干预措施: Core needle biopsy (Procedure)
Placebo
Placebo Comparator
- Subcutaneous injection of the placebo at a dose of 60 mg at two time points: baseline and 6 months
- Participants will also be instructed to take calcium and vitamin D supplements daily for 12 months between baseline examination and 12 month mammographic breast density examination
- Mammographic breast density will be assessed at three time points in all participants: baseline, 12 months, and 24 months. A 36 month optional assessment may also occur.
- Biopsies and blood draws will occur for research purposes at baseline and 12 months.
干预措施: Blood draw (Procedure)
结局指标
主要结局
Change in mammographic breast density between the two arms as measured by volumetric percent density
时间窗: From baseline to 12 months
-The investigators will use volumetric percent density (VPD) as the primary mammographic breast density measure.
次要结局
- Change in mammographic breast density between the two arms as measured by volumetric percent density(From 12 months to 24 months)
- Change in expression gene related to RANK in breast tissue compared between the two arms(Baseline and 12 months)
- Change in expression gene related to progesterone in breast tissue compared between the two arms(Baseline and 12 months)
- Change in expression gene related to metabolics in breast tissue compared between the two arms(Baseline and 12 months)
- Change in expression gene related to immune in breast tissue compared between the two arms(Baseline and 12 months)
- Change in expression gene related to inflammatory in breast tissue compared between the two arms(Baseline and 12 months)
- Change in expression of markers of breast epithelial and stromal proliferation compared between the two arms(Baseline and 12 months)
- Change in breast metabolome compared between the two arms(Baseline and 12 months)
研究者
研究点 (1)
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