RANKL Inhibition and Mammographic Breast Density

Dense Breasts Clinical Trial

— TRIDENT  

Official title:

Randomized Clinical Trial of RANKL Inhibition With Denosumab on Mammographic Density in Premenopausal Women With Dense Breasts (TRIDENT)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04067726
• Other study ID #: 201907039
• Status: Recruiting
• Phase: Phase 2
• Start date: August 27, 2019
• Est. completion date: August 31, 2026

Study information

• Verified date: April 2024
• Source: Washington University School of Medicine
• Contact: Adetunji T Toriola, M.D., Ph.D. MPH
• Phone: 314-286-2668
• Email: a.toriola[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. completion date: August 31, 2026
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Dense Breasts

Intervention

Drug:
• Denosumab
Denosumab is commercially available and will be provided at no cost to participants.
• Placebo
Placebo will be made available as 1 mL sterile, non-pyrogenic water solution in a single-use prefilled syringe.
• 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.
• 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.

Procedure:
• Core needle biopsy
Baseline and 12 months
• Blood draw
Baseline and 12 months

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in expression of RANKL pathway genes compared between the two arms		Baseline and 12 months
Other	Change in expression of progesterone receptor and progesterone-regulated pathway genes compared between the two arms		Baseline and 12 months
Other	Change in expression of markers of epithelial proliferation compared between the two arms		Baseline and 12 months
Other	Change in expression of markers of stromal proliferation and growth factors compared between the two arms		Baseline and 12 months
Other	Change in expression of immune markers compared between the two arms		Baseline and 12 months
Other	Change in expression of inflammatory markers compared between the two arms		Baseline and 12 months
Other	Correlations between gene expression within the breast tissue and within the blood		Baseline
Primary	Change in mammographic breast density between the two arms as measured by volumetric percent density	-The investigators will use volumetric percent density (VPD) as the primary mammographic breast density measure.	From baseline to 12 months
Secondary	Change in mammographic breast density between the two arms as measured by volumetric percent density		From baseline to 24 months
Secondary	Change in mammographic breast density between the two arms as measured by volumetric percent density		From 12 months to 24 months

External Links

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