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Monoclonal Antibodies

RANKL Inhibition for Dense Breasts (TRIDENT Trial)

Phase 2

Waitlist Available

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

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

At least 40 years of age.

Female.

Must not have

History of ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), invasive breast cancer, or other cancer (except non-melanoma skin cancer).

History of osteoporosis or severe osteopenia.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline and 12 months

Summary

This trial will test whether or not a drug that inhibits RANKL decreases mammographic density in high-risk premenopausal women with dense breasts, which could lead to new ways to prevent breast cancer.

Who is the study for?

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.

What is being tested?

The 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.

What are the potential side effects?

Potential side effects may include issues related to bone health such as osteonecrosis of the jaw, infection risks due to immune system changes from denosumab, and common drug-related reactions like fatigue or skin rash.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 40 years old or older.

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I am female.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have been diagnosed with osteoporosis or severe osteopenia.

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I have ongoing dental issues or upcoming oral surgery.

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I am currently taking tamoxifen, aromatase inhibitors, bisphosphonates, or RANKL inhibitors.

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I have had bone disease in my jaw.

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I have a known BRCA mutation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline and 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline and 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline and 12 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in mammographic breast density between the two arms as measured by volumetric percent density

Other study objectives

Change in expression of RANKL pathway genes compared between the two arms

Change in expression of immune markers compared between the two arms

Change in expression of inflammatory markers compared between the two arms

+4 more

Side effects data

From 2022 Phase 4 trial • 37 Patients • NCT04026256

44%

joint pain

22%

nausea

22%

propagation of fracture at biopsy site

11%

dizziness

11%

rhinorrhea

100%

80%

60%

40%

20%

Study treatment Arm

Denosumab Only

Teriparatide Only

Denosumab and Teriparatide

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Blood draw

2021

Completed Phase 4

~7380

Calcium

2014

Completed Phase 4

~4660