Effect of Denosumab on Cellular Biomarkers in the Human Breast

Study Overview
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Brief Summary
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To evaluate whether administration of denosumab results in a decrease compared to the control group in proliferation of mammary epithelial cells as measured by the Ki-67 proliferation index.

Official Title
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A Randomized, Stratified, Open-label, No-treatment-controlled, Parallel Group, Multicenter Phase 1 Trial to Evaluate the Effect of Denosumab on Cellular Proliferation in the Human Breast

Conditions
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Healthy Volunteer, Female, Breast

Intervention / Treatment
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* Drug: Denosumab
* Procedure: Percutaneous core needle breast biopsy


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Willing to use, in combination with her partner, 2 non-hormonal methods of effective contraception or practice sexual abstinence. Subjects who are surgically sterile (eg, history of hysterectomy) or whose sexual partner is sterile (eg, history of vasectomy) are not required to use contraceptive measures Laboratory tests are within clinically acceptable range Clinically acceptable physical exam and no history or evidence of any clinically significant medical disorder that would pose a risk to subject safety or interfere with study evaluations or procedures. EXCLUSION CRITERIA: Female subject with a prior history of breast cancer; breast implant in the breast to be biopsied; Known history of fibrocystic breast disease Subject is unable or unwilling to provide breast biopsy tissue from the upper outer quadrant of her breast Pregnant or plans to become pregnant while exposed to investigational product Lactating/breastfeeding or plans to breastfeed while exposed to investigational product Recent use of any non-approved medications or devices Uncontrolled thyroid disorder Significant dental/oral disease Planned invasive dental procedures Positive urine screen for alcohol and/or drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: No treatment<br>Participants received no treatment and underwent percutaneous core needle breast biopsies on Day 1 and Day 28. | Procedure: Percutaneous core needle breast biopsy<br> <br> |
| Experimental: Denosumab 60 mg<br>Participants received 60 mg denosumab by subcutaneous injection on Day 1 and underwent percutaneous core needle breast biopsies on Day 1 (prior to study treatment) and Day 28. | Drug: Denosumab<br>* Single sucutaneous dose<br>Procedure: Percutaneous core needle breast biopsy<br> <br> |
| Experimental: Denosumab 120 mg<br>Participants received 120 mg denosumab by subcutaneous injection on Day 1 and underwent percutaneous core needle breast biopsies on Day 1 (prior to study treatment) and Day 28. | Drug: Denosumab<br>* Single sucutaneous dose<br>Procedure: Percutaneous core needle breast biopsy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Log Ratio of Post-baseline to Baseline Ki-67 Index in Mammary Epithelial Cells | Ki-67 is a marker for cell proliferation. Participants underwent percutaneous core needle breast biopsies on Day 1 (Baseline, prior to treatment) and Day 28. Levels of Ki67 were measured using immunohistochemical staining and digital imaging. The proliferation index was calculated as the percentage of Ki-67 positive terminal ductal lobular unit (TDLU) and duct epithelial cells. The higher the percentage, the higher the rate of epithelial cell proliferation. | Baseline and Day 28 |