search
Back to results

RANKL Inhibition and Breast Tissue Biomarkers

Primary Purpose

Breast Cancer Prevention, Mammographic Density

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ultrasound-guided core needle biopsy
Denosumab
Blood draw
Calcium
Vitamin D
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Breast Cancer Prevention focused on measuring Mammographic density, Premenopausal, Breast cancer, Chemoprevention, Denosumab

Eligibility Criteria

35 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Female.
  • Premenopausal.
  • At least 35 years of age.
  • Dense breasts on routine mammogram.
  • Willing to take calcium (1,200mg) and vitamin D (800 IU) daily.

  • At increased risk for breast cancer using any of the following:

    • Positive family history of breast cancer
    • Breast cancer risk prediction models
  • Able and willing to return for repeat biopsy.
  • Able to understand and willing to sign an IRB-approved written informed consent document.

Exclusion Criteria:

  • Current use of tamoxifen, aromatase inhibitors, or bisphosphonates.
  • Concurrently participating in another cancer chemoprevention trial (unless no longer receiving the intervention).
  • Pregnant or lactating.
  • Recent tooth extraction or dental procedure.
  • Unhealed and/or planned dental/oral surgery.
  • History of osteonecrosis/osteomyelitis of the jaw.
  • History of osteoporosis or severe osteopenia.
  • Unable/unwilling to return for repeat biopsy.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Denosumab

Arm Description

An ultrasound-guided core needle breast biopsy will be performed on day 1 prior to the intervention. A single dose of subcutaneous denosumab 60mg will be administered immediately after the core biopsy on day 1. This will take place on an outpatient basis. Repeat core-needle biopsy will take place on Day 60 (+/-10 days). Blood samples will also be collected at the time of core-needle biopsy to allow for biomarker assay. Gene expression analyses will be done using NanoString nCounter gene expression system.

Outcomes

Primary Outcome Measures

Effect of denosumab on breast tissue gene RANK pathway gene expression
-The investigators will evaluate changes in RANK pathway gene expression between baseline and day 60 using NanoString NCounter platform
Effect of denosumab on breast tissue gene expression in progesterone-regulated pathways
The investigators will evaluate changes in progesterone-regulated pathways gene expression between baseline and day 60 using NanoString NCounter platform.
Effect of denosumab on breast tissue breast tissue ki-67 proliferation
The investigators will evaluate changes in ki-67 proliferation between baseline and day 60 using immunohistochemistry
Effect of denosumab on breast stromal proliferation
The investigators will evaluate changes in gene expression of markers of stromal proliferation between baseline and day 60 using NanoString NCounter platform.

Secondary Outcome Measures

Correlation of breast tissue RANK pathway gene expression with circulating biomarker levels

Full Information

First Posted
August 1, 2018
Last Updated
April 10, 2020
Sponsor
Washington University School of Medicine
search

1. Study Identification

Unique Protocol Identification Number
NCT03629717
Brief Title
RANKL Inhibition and Breast Tissue Biomarkers
Official Title
RANKL Inhibition and Breast Tissue Biomarkers in Premenopausal Women With Dense Breasts
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
June 1, 2018 (Actual)
Primary Completion Date
December 3, 2018 (Actual)
Study Completion Date
December 3, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A robust knowledge of how to reduce breast density could play a key role in breast cancer prevention in premenopausal women, but viable preventative targets to reduce breast density-associated breast cancer risk are yet to be developed. The investigators propose to investigate the effect of RANKL inhibition with denosumab on breast tissue markers in high-risk premenopausal women with dense breasts. Study findings could provide robust evidence to move forward with a clinical trial targeting RANKL inhibition in premenopausal breast cancer prevention.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer Prevention, Mammographic Density
Keywords
Mammographic density, Premenopausal, Breast cancer, Chemoprevention, Denosumab

7. Study Design

Primary Purpose
Prevention
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Denosumab
Arm Type
Experimental
Arm Description
An ultrasound-guided core needle breast biopsy will be performed on day 1 prior to the intervention. A single dose of subcutaneous denosumab 60mg will be administered immediately after the core biopsy on day 1. This will take place on an outpatient basis. Repeat core-needle biopsy will take place on Day 60 (+/-10 days). Blood samples will also be collected at the time of core-needle biopsy to allow for biomarker assay. Gene expression analyses will be done using NanoString nCounter gene expression system.
Intervention Type
Procedure
Intervention Name(s)
Ultrasound-guided core needle biopsy
Intervention Description
Tissue collection for this research proposal will be used for research purposes only and will not inform participant care
Intervention Type
Drug
Intervention Name(s)
Denosumab
Other Intervention Name(s)
Xgeva, Prolia
Intervention Description
Denosumab is a human IgG2 monoclonal antibody with affinity and specificity for human RANKL
Intervention Type
Procedure
Intervention Name(s)
Blood draw
Intervention Description
20 mL of fasting whole blood will be collected before denosumab (Day 1) and one month after denosumab administration (day 60 +/- 10 days)
Intervention Type
Drug
Intervention Name(s)
Calcium
Intervention Description
1200mg daily
Intervention Type
Drug
Intervention Name(s)
Vitamin D
Intervention Description
800 IU daily
Primary Outcome Measure Information:
Title
Effect of denosumab on breast tissue gene RANK pathway gene expression
Description
-The investigators will evaluate changes in RANK pathway gene expression between baseline and day 60 using NanoString NCounter platform
Time Frame
Between baseline and day 60
Title
Effect of denosumab on breast tissue gene expression in progesterone-regulated pathways
Description
The investigators will evaluate changes in progesterone-regulated pathways gene expression between baseline and day 60 using NanoString NCounter platform.
Time Frame
Between baseline and day 60
Title
Effect of denosumab on breast tissue breast tissue ki-67 proliferation
Description
The investigators will evaluate changes in ki-67 proliferation between baseline and day 60 using immunohistochemistry
Time Frame
Between baseline and day 60
Title
Effect of denosumab on breast stromal proliferation
Description
The investigators will evaluate changes in gene expression of markers of stromal proliferation between baseline and day 60 using NanoString NCounter platform.
Time Frame
Between baseline and day 60
Secondary Outcome Measure Information:
Title
Correlation of breast tissue RANK pathway gene expression with circulating biomarker levels
Time Frame
60 days

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female. Premenopausal. At least 35 years of age. Dense breasts on routine mammogram. Willing to take calcium (1,200mg) and vitamin D (800 IU) daily. At increased risk for breast cancer using any of the following: Positive family history of breast cancer Breast cancer risk prediction models Able and willing to return for repeat biopsy. Able to understand and willing to sign an IRB-approved written informed consent document. Exclusion Criteria: Current use of tamoxifen, aromatase inhibitors, or bisphosphonates. Concurrently participating in another cancer chemoprevention trial (unless no longer receiving the intervention). Pregnant or lactating. Recent tooth extraction or dental procedure. Unhealed and/or planned dental/oral surgery. History of osteonecrosis/osteomyelitis of the jaw. History of osteoporosis or severe osteopenia. Unable/unwilling to return for repeat biopsy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adetunji T Toriola, M.D., Ph.D., MPH
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

RANKL Inhibition and Breast Tissue Biomarkers

We'll reach out to this number within 24 hrs