Denosumab and MRI Breast Imaging (Dmab)

August 20, 2024 updated by: Alison Stopeck

Phase II Correlative Study of Denosumab Effects on Tissue and Imaging Breast Biomarkers

This is a non-randomized phase II trial of denosumab at 120 mg subcutaneous injection monthly in pre- and post-menopausal women diagnosed with stage 0-III breast cancer who are currently not receiving anticancer treatment with hormonal therapies, chemotherapy, or radiation. All patients will undergo quantification of breast density by MRI at baseline and after 6 months on denosumab. Because the therapeutic agent is an injectable drug, the investigators will conduct a single arm study with both pre- and post-treatment measurements to determine the extent of variability in breast density over time and a placebo treatment period or group will not be utilized. This is an investigator initiated trial and Amgen (SPONSOR) will provide the trial drug denosumab.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

According to the results of several studies footnoted in this protocol, there is now convincing evidence that extensive areas of radiographically-dense tissue in the breast is an independent risk factor for the development of breast cancer. Here, the investigators postulate that it is RANK ligand that mediates the association between breast density and risk of breast cancer for which progesterone is one of several factors that influence the availability of RANK ligand in mammary tissue to promote or sustain higher breast density. As such, the investigators hypothesize that inhibition of RANK ligand with the anti-RANK ligand antibody therapeutic agent denosumab will decrease breast density; a risk factor for breast cancer development. The investigators will test the primary hypothesis that RANK ligand inhibition by denosumab (Xgeva) given 120mg monthly to pre- and post-menopausal breast cancer patients will significantly decrease breast density over 6 months. Breast density will be assessed by magnetic resonance fat water imaging (MR-FW) of the breast. At the beginning of the study participants will be measured for a change in breast density by MRI between baseline 1 and baseline 2 (end of 3 months observation period). All patients will then receive 6 months of 120 mg denosumab subcutaneously every month with repeat MR imaging to obtain measurements after 6 months on denosumab. All participants will be asked to provide an optional core needle breast biopsy sample at baseline and after 6 months on denosumab.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
42

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 71 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pre or postmenopausal women with first incidence of early stage (stages 0 - III) breast cancer who have completed all treatment and are cancer-free, which includes women at high risk for developing invasive cancer i.e. having a breast biopsy positive for atypical ductal or lobular hyperplasia or carcinoma in situ.
  • Age ≤ 75 years
  • 44 patients will be accrued as follows: a) 22 evaluable patients will be premenopausal as defined as regular menses (24-38 days) b) 22 evaluable patients will be postmenopausal as defined by a history of amenorrhea for at least one year or hormone levels (estradiol/FSH) consistent with menopause if post-hysterectomy status, or history of surgical/medical castration.
  • Normal serum calcium or albumin-adjusted serum calcium between 2.0 and 2.9 mmol/L (8.0-11.5mg/dL).
  • Adequate vitamin D level (25-hydroxy vitamin D level > 20 ng/mL)
  • Currently on no active treatment for breast cancer and at least 3 months post all the treatments, with the exception of aromatase inhibitors (exemestane, anastrozole, letrozole)
  • No prior or current use of IV bisphosphonates
  • No current use of oral bisphosphonates
  • Patients must have an unaffected, non-irradiated contralateral breast
  • Significant breast density as determined by mammography and defined by the descriptive terms scattered fibroglandular tissue/densities, heterogeneously dense, or mostly dense tissue in the mammography report.
  • Adequate renal function defined as a serum creatinine < 1.5 x ULN or CrCl > 30mL/min
  • A willingness and ability to follow the study protocol, as indicated by provision of informed consent to participate
  • Willingness to being tested for current pregnancy and use of birth control while being treated with denosumab (pre-menopausal women only)

Exclusion Criteria:

  • Age > 75 years
  • Subject has known sensitivity to any of the products to be administered during the study (e.g., mammalian derived products, denosumab, calcium, or vitamin D).
  • Patients have prior history or current evidence of osteonecrosis or osteomyelitis of the jaw.
  • Patients have active dental or jaw condition which requires oral surgery, including tooth extraction.
  • Patients have non-healed dental or oral surgery, including tooth extraction.
  • Patients with planned invasive dental procedures
  • Subject is pregnant or breast feeding, or planning to become pregnant within 5 months after the end of the treatment
  • Subject is of child bearing potential and is not willing to use, in combination with her partner, highly effective methods of contraception or abstinence during treatment and for 5 months after the end of treatment
  • Active infection with Hepatitis B, Hepatitis C, or Human Immunodeficiency virus (HIV)
  • Any condition or disorder that compromises the ability of the subject to provide written informed consent and/or comply with study procedures
  • History of claustrophobia
  • Have electrically, magnetically, or mechanically activated implants including cardiac pacemaker, cochlear implants, magnetic surgical clips or prostheses.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Denosumab
6 monthly subcutaneous injections of denosumab
Drug: Denosumab
monthly subcutaneous injections
Other Names:
  • XGEVA

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Relative Change of ≥ 5% in Breast Density at 6 Months
Time Frame: baseline, 6 months
Breast density will be measured via non-contrast MRI before and after 6 months on denosumab
baseline, 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Absolute Change > 1% in Breast Density
Time Frame: 6 months
Unadjusted Absolute Change > 1% in breast density
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Alison Stopeck

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Amgen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Alison Stopeck, MD, Stony Brook University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 20, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 20, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 20, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 23, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 24, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 23, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 20, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 706513

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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