RANKL Inhibition and Breast Tissue Biomarkers

Mammographic Density Clinical Trial

Official title:

RANKL Inhibition and Breast Tissue Biomarkers in Premenopausal Women With Dense Breasts

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03629717
• Other study ID #: 201801105
• Status: Completed
• Phase: Early Phase 1
• Start date: June 1, 2018
• Est. completion date: December 3, 2018

Study information

• Verified date: April 2020
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 3, 2018
• Est. primary completion date: December 3, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 35 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer Prevention
• Breast Neoplasms
• Mammographic Density

Intervention

Procedure:
• Ultrasound-guided core needle biopsy
Tissue collection for this research proposal will be used for research purposes only and will not inform participant care

Drug:
• Denosumab
Denosumab is a human IgG2 monoclonal antibody with affinity and specificity for human RANKL

Procedure:
• Blood draw
20 mL of fasting whole blood will be collected before denosumab (Day 1) and one month after denosumab administration (day 60 +/- 10 days)

Drug:
• Calcium
1200mg daily
• Vitamin D
800 IU daily

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Between baseline and day 60
Primary	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.	Between baseline and day 60
Primary	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	Between baseline and day 60
Primary	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.	Between baseline and day 60
Secondary	Correlation of breast tissue RANK pathway gene expression with circulating biomarker levels		60 days

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine