RANKL Inhibition for Dense Breasts
(TRIDENT Trial)

Recruiting in Palo Alto (17 mi)

Overseen byAdetunji T Toriola, M.D., Ph.D., MPH

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Washington University School of Medicine

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Research Team

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

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for premenopausal women at least 40 years old with dense breasts, as shown on a mammogram. Participants must be able to consent and not have a history of certain breast conditions or cancer, known BRCA mutations, or be using related medications. They should not be pregnant or planning pregnancy during the trial.

Inclusion Criteria

Dense breasts on routine mammogram (BI-RADS Category C and D, i.e. volumetric percent density ≥ 7.5% on Volpara)

I am 40 years old or older.

Able to understand and willing to sign an IRB-approved written informed consent document.

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Exclusion Criteria

I have a history of breast cancer or another type of cancer, except for non-melanoma skin cancer.

Concurrent participation in another cancer chemoprevention trial (unless no longer receiving the intervention).

I have been diagnosed with osteoporosis or severe osteopenia.

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Treatment Details

Interventions

Denosumab (Monoclonal Antibodies)

Trial OverviewThe study tests if RANKL inhibition with denosumab can reduce mammographic density in high-risk women with dense breasts. It also examines its effect on proliferation markers and breast cancer risk biomarkers. The trial includes blood draws, biopsies, and supplements like calcium and vitamin D3.

Participant Groups

2Treatment groups

Experimental Treatment

Placebo Group

Group I: DenosumabExperimental Treatment5 Interventions

* 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 II: PlaceboPlacebo Group5 Interventions

* 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 is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺 Approved in European Union as Prolia for:

Osteoporosis in postmenopausal women
Bone loss associated with hormone ablation therapy for prostate cancer
Bone loss associated with hormone ablation therapy for breast cancer

🇺🇸 Approved in United States as Prolia for:

Treatment of postmenopausal women with osteoporosis at high risk for fracture
Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

🇨🇦 Approved in Canada as Prolia for:

Treatment of osteoporosis in postmenopausal women at high risk for fracture
Treatment to increase bone mass in men with osteoporosis at high risk for fracture

🇯🇵 Approved in Japan as Prolia for: