Clinical Trials /

Denosumab and MRI Breast Imaging

NCT02613416

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Denosumab and MRI Breast Imaging
  • Official Title: Phase II Correlative Study of Denosumab Effects on Tissue and Imaging Breast Biomarkers

Clinical Trial IDs

  • ORG STUDY ID: 706513
  • NCT ID: NCT02613416

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
DenosumabXGEVADenosumab

Purpose

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 1, baseline 2 (after 3-month observation period) and after 3 and 6 months on denosumab, which means after 0, 3, 6 and 9 months after entering the study. 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.

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. To
      control for the variability in the endpoints, subjects will undergo an observational period
      of 3 months (no denosumab), at the end of which they will be measured for a change in breast
      density by MRI between baseline 1 and baseline 2 (end of 3 months observation period). The
      change in breast density from the baseline MRI to the first follow-up MRI at 3 months on
      study but not on intervention will provide a baseline breast density measurement for
      determining change in breast density in women on intervention for 6 months. All patients
      will then receive 6 months of 120 mg denosumab subcutaneously every month with repeat MR
      imaging to obtain measurements after 3 and 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.
    

Trial Arms

NameTypeDescriptionInterventions
DenosumabExperimental6 monthly subcutaneous injections of denosumab
  • Denosumab

Eligibility Criteria

        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.

          -  Osteopenia as defined by a bone density T-score of at least -1.0 in the spine, hip,
             or femoral neck

          -  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

          -  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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:N/A
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Breast Density
Time Frame:6 months
Safety Issue:
Description:Breast density will be measured via non-contrast MRI before and after 6 months on denosumab

Secondary Outcome Measures

Measure:Blood markers
Time Frame:6 months
Safety Issue:
Description:Change in progestogen levels and the OPG/RANKL ratio after 6 months on denosumab

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Stony Brook University

Last Updated

October 13, 2016