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RANKL Inhibition and Mammographic Breast Density (TRIDENT)

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The Washington University

Status and phase

Active, not recruiting
Phase 2

Conditions

Dense Breasts

Treatments

Procedure: Core needle biopsy
Drug: Placebo
Procedure: Blood draw
Drug: Vitamin D3
Drug: Denosumab
Drug: Calcium

Study type

Interventional

Funder types

Other
NIH

Identifiers

NCT04067726
201907039

Details and patient eligibility

About

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.

Enrollment

210 patients

Sex

Female

Ages

40+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

210 participants in 2 patient groups, including a placebo group

Denosumab
Experimental group
Description:
* 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.
Treatment:
Drug: Calcium
Drug: Denosumab
Drug: Vitamin D3
Procedure: Blood draw
Procedure: Core needle biopsy
Placebo
Placebo Comparator group
Description:
* 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.
Treatment:
Drug: Calcium
Drug: Vitamin D3
Procedure: Blood draw
Drug: Placebo
Procedure: Core needle biopsy

Trial documents
1

Trial contacts and locations

1

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Central trial contact

Suleepon (Emmy) Uttamapinan, M.D., MSc.; Adetunji T Toriola, M.D., Ph.D. MPH

Data sourced from clinicaltrials.gov

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