RANKL Inhibition and Mammographic Breast Density

NCT ID: NCT04067726

Last Updated: 2025-10-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-27
• Study Completion Date: 2026-08-31

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 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.

Conditions

Dense Breasts

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

Denosumab is commercially available and will be provided at no cost to participants.

Calcium

Intervention Type: DRUG

-Participants will be instructed to take calcium (at least 500 mg) daily for 12 months between baseline examination and 12- month mammographic breast density examination.

Vitamin D3

Intervention Type: DRUG

Participants will be instructed to take vitamin D3 (at least 400 IU) supplements daily for 12 months between baseline examination and 12- month mammographic breast density examination.

Core needle biopsy

Intervention Type: PROCEDURE

Baseline and 12 months

Blood draw

Intervention Type: PROCEDURE

Baseline and 12 months

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be made available as 1 mL sterile, non-pyrogenic water solution in a single-use prefilled syringe.

Calcium

Intervention Type: DRUG

-Participants will be instructed to take calcium (at least 500 mg) daily for 12 months between baseline examination and 12- month mammographic breast density examination.

Vitamin D3

Intervention Type: DRUG

Participants will be instructed to take vitamin D3 (at least 400 IU) supplements daily for 12 months between baseline examination and 12- month mammographic breast density examination.

Core needle biopsy

Intervention Type: PROCEDURE

Baseline and 12 months

Blood draw

Intervention Type: PROCEDURE

Baseline and 12 months

Interventions

Denosumab

Denosumab is commercially available and will be provided at no cost to participants.

Intervention Type: DRUG

Placebo

Placebo will be made available as 1 mL sterile, non-pyrogenic water solution in a single-use prefilled syringe.

Intervention Type: DRUG

Calcium

-Participants will be instructed to take calcium (at least 500 mg) daily for 12 months between baseline examination and 12- month mammographic breast density examination.

Intervention Type: DRUG

Vitamin D3

Participants will be instructed to take vitamin D3 (at least 400 IU) supplements daily for 12 months between baseline examination and 12- month mammographic breast density examination.

Intervention Type: DRUG

Core needle biopsy

Baseline and 12 months

Intervention Type: PROCEDURE

Blood draw

Baseline and 12 months

Intervention Type: PROCEDURE

Other Intervention Names

Prolia

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adetunji T Toriola, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

201907039

Identifier Type: -

Identifier Source: org_study_id