RANKL Inhibition and Mammographic Breast Density

Phase 2

Active, not recruiting

• Conditions: Dense Breasts
• Interventions: Drug: Placebo; Drug: Denosumab; Drug: Calcium; Drug: Vitamin D3; Procedure: Core needle biopsy; Procedure: Blood draw

• Registration Number: NCT04067726
• Lead Sponsor: Washington University School of Medicine

Brief Summary

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 mammograph...

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-08-16
• Study First Submitted QC: 2019-08-21
• Study First Posted: 2019-08-26
• Study Start: 2019-08-27
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-28
• Last Update Posted: 2024-10-31
• Primary Completion: 2025-08-31
• Study Completion: 2026-08-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 210

Inclusion Criteria

• Female.
• 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.

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Exclusion Criteria

• 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Denosumab	Core needle biopsy	* 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.
Placebo	Core needle biopsy	* 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.
Placebo	Placebo	* 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.
Placebo	Blood draw	* 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.
Denosumab	Blood draw	* 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.
Denosumab	Denosumab	* 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.
Denosumab	Vitamin D3	* 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.
Denosumab	Calcium	* 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.
Placebo	Vitamin D3	* 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.
Placebo	Calcium	* 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.

Primary Outcome Measures

Name	Time	Method
Change in mammographic breast density between the two arms as measured by volumetric percent density	From baseline to 12 months	-The investigators will use volumetric percent density (VPD) as the primary mammographic breast density measure.

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States