Denosumab for Decreasing Breast Density in High Risk Premenopausal Women with Dense Breasts

Status: Active

Description

This phase II trial studies how well denosumab works in decreasing breast density in premenopausal women with dense breasts who have a high risk of developing breast cancer. Having dense breasts is associated with an increased risk of developing breast cancer, therefore reducing breast density may decrease this risk. Denosumab is a monoclonal antibody that may reduce breast density by blocking progesterone associated cell growth in breast tissue.

Eligibility Criteria

Inclusion Criteria

  • Premenopausal
  • Dense breasts on routine mammogram (volumetric percent density >= 7.5% on Volpara, equivalent to Breast Imaging Reporting and Data System [BI-RADS)] category C)
  • May be at increased risk for breast cancer using any of the following: * Positive family history of breast cancer in a first-degree relative. * Presence of non-BRCA susceptibility genes (e.g. ATM, BARD1, CDH1, CHEK2, MSH6, PALB2, PTEN, RAD51D, and TP53). * Biopsy confirmed benign breast disease. * Age at first birth > 30 years. * Nulliparity. * Rosner-Colditz risk prediction model.
  • Able to understand and willing to sign an Institutional Review Board (IRB)-approved written informed consent document

Exclusion Criteria

  • History of ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), invasive breast cancer, or other cancer (except non-melanoma skin cancer)
  • Known BRCA mutation(s)
  • Current use of tamoxifen, aromatase inhibitors, bisphosphonates, or RANKL inhibitors
  • Concurrent participation in another cancer chemoprevention trial (unless no longer receiving the intervention)
  • Pregnant or lactating, or planning to get pregnant while the trial is ongoing
  • Recent history of invasive dental procedure (e.g. tooth extraction, dental implant, oral surgery)
  • Unhealed and/or planned dental/oral surgery
  • History of osteonecrosis/osteomyelitis of the jaw
  • History of osteoporosis or severe osteopenia

Locations & Contacts

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Contact: Adetunji T Toriola
Phone: 314-286-2668
Email: a.toriola@wustl.edu

Trial Objectives and Outline

PRIMARY OBJECTIVE:

I. Quantify the effect of RANKL inhibition with denosumab on mammographic density in high-risk premenopausal women with dense breasts.

EXPLORATORY OBJECTIVES:

I. Determine the effect of RANKL inhibition on expression of RANK pathway genes.

II. Determine the effect of RANKL inhibition on expression of progesterone receptor (PgR) and progesterone-regulated pathway genes.

III. Determine the effect of RANKL inhibition on markers of epithelial proliferation.

IV. Determine the effect of RANKL inhibition on markers of stromal proliferation and growth factors.

V. Determine the effect of RANKL inhibition on gene expression of immune markers.

VI. Determine the effect of RANKL inhibition on gene expression of inflammatory markers.

VII. Evaluate correlations between gene expression within the breast tissues and within the blood.

VIII. Predict response to denosumab using the biomarkers evaluated in the exploratory objectives.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive denosumab subcutaneously (SC) at baseline and at 6 months. Patients also receive calcium and cholecalciferol orally (PO) once daily (QD) for up to 12 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo SC at baseline and at 6 months. Patients also receive calcium and cholecalciferol orally PO once daily QD for up to 12 months in the absence of disease progression or unacceptable toxicity.

Patients are followed up every 2 months for 12 months during the study, and then at 24 and 36 months.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Prevention

Lead Organization

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Adetunji T Toriola

Trial IDs

Primary ID 201907039
Secondary IDs NCI-2019-05947
Clinicaltrials.gov ID NCT04067726