RANKL Inhibition and Breast Tissue Biomarkers

NCT03629717 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: 201801105
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer Prevention; Mammographic Density

Keywords

Mammographic density; Premenopausal; Breast cancer; Chemoprevention; Denosumab

Outcome Measures

Primary Outcomes (3)

• Effect of denosumab on breast tissue gene pathway gene expression

  The investigators will evaluate changes in pathway gene expression between baseline and day 60 using NanoString NCounter platform

  Between baseline and day 60

• Effect of denosumab on pathways that may influence breast cancer development as measured by spatial transcriptomic analysis

  The investigators will evaluate changes in breast tissue spatial transcriptomics.

  Between baseline and day 60

• Effect of denosumab on pathways that may influence breast cancer development as measured by metabolomic analysis

  The investigators will evaluate changes in metabolomics.

  Between baseline and day 60

Secondary Outcomes (1)

• Correlation of breast tissue gene expression with circulating biomarker levels

  60 days

Study Arms (1)

Denosumab

EXPERIMENTAL

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.

Procedure: Ultrasound-guided core needle biopsy; Drug: Denosumab; Procedure: Blood draw; Drug: Calcium; Drug: Vitamin D

Interventions

Ultrasound-guided core needle biopsy PROCEDURE

Tissue collection for this research proposal will be used for research purposes only and will not inform participant care

Denosumab

Denosumab DRUG

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

Also known as: Xgeva, Prolia

Denosumab

Blood draw PROCEDURE

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

Denosumab

Calcium DRUG

1200mg daily

Denosumab

Vitamin D DRUG

800 IU daily

Denosumab

Eligibility Criteria

• Age: 35 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Denosumab; Blood Specimen Collection; Calcium; Vitamin D

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Adetunji T Toriola, M.D., Ph.D., MPH

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2018
• First Posted: August 14, 2018
• Study Start: June 1, 2018
• Primary Completion: December 3, 2018
• Study Completion: December 3, 2018
• Last Updated: October 16, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)