Effect of Denosumab on Cellular Biomarkers in the Human Breast

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer, Female, Breast
• Intervention / Treatment: Procedure: Percutaneous core needle breast biopsy; Drug: Denosumab

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • Research Site
  • Florida
    • Hollywood, Florida, United States, 33024
      • Research Site
    • Miami, Florida, United States, 33143
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: No treatment; Participants received no treatment and underwent percutaneous core needle breast biopsies on Day 1 and Day 28.	Procedure: Percutaneous core needle breast biopsy
Experimental: Denosumab 60 mg; 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.	Procedure: Percutaneous core needle breast biopsy; Drug: Denosumab; Single sucutaneous dose
Experimental: Denosumab 120 mg; 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.	Procedure: Percutaneous core needle breast biopsy; Drug: Denosumab; Single sucutaneous dose

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: February 25, 2014
• First Submitted That Met QC Criteria: March 25, 2014
• First Posted (Estimate): March 31, 2014

Study Record Updates

• Last Update Posted (Estimate): September 24, 2015
• Last Update Submitted That Met QC Criteria: August 24, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: 20130349