Clinical Trials /

Presurgical Trial of Denosumab in Breast Cancer

NCT02900469

Description:

The purpose of this study is to determine whether one dose of denosumab can lead to changes in the tumor, which may decrease the ability of tumor to spread.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Presurgical Trial of Denosumab in Breast Cancer
  • Official Title: Pre-surgical Evaluation of Denosumab in Patients With Operable Invasive Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: s14-01311
  • NCT ID: NCT02900469

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
denosumabXgevaDenosumab & surgery

Purpose

The purpose of this study is to determine whether one dose of denosumab can lead to changes in the tumor, which may decrease the ability of tumor to spread.

Detailed Description

      Breast cancer is the most common cancer among women, affecting one in eight women, and is
      the second leading cause of mortality from cancer. Bone metastases are a frequent
      complication of breast cancer, and the mechanism of breast cancer metastases to bone is an
      ongoing area of research.. Receptor activator of NF-kB (RANK) and its ligand (RANKL) have
      been identified and characterized for its role in bone remodeling. RANKL is a member of the
      tumor necrosis factor (TNF) family of cytokines that binds to its receptor RANK to control
      osteoclast differentiation, activation, and survival. RANK protein expression is not only
      found on osteoclasts and dendritic cells but also on T cells and mammary epithelial cells.
      RANK and RANKL is important for lymph node and thymus formation as well as lactating mammary
      gland development during pregnancy. Furthermore, the RANK/RANKL axis has been linked to
      progestin driven breast carcinomas and bone metastases.

      RANK is expressed in 6-57% of invasive human breast cancers (depending upon the parameters
      for defining positivity and antibodies utilized for immunohistochemistry (IHC)), and RANKL
      driven hormone (progesterone -dependent proliferation, survival, and nonproliferative
      expansion of mammary stem cells may contribute to breast cancer initiation, progression, and
      recurrence.

      We hypothesize that denosumab can inhibit RANKL signaling in early breast tumors which
      express RANK, inhibiting pro-metastatic mechanisms and reducing immunosuppression in the
      tumor microenvironment. This will be tested in a pre-surgical clinical trial (Phase 0) to
      evaluate and select the pharmacodynamics markers of RANKL inhibition in breast cancer.
    

Trial Arms

NameTypeDescriptionInterventions
Denosumab & surgeryExperimentaldenosumab: 120 mg subcutaneous injection Surgery: 2-4 weeks after denosumab

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Patients must have histologically confirmed invasive breast cancer (stages I-III) who
                 have undergone core needle biopsy (clinically or radiographically at least T1c to
                 allow adequate residual cancer tissue at surgery) and will be scheduled for surgical
                 resection (i.e. segmental excision or mastectomy).
    
              -  Archival tissue freshly cut from core biopsy must be available; patients who had a
                 diagnostic core biopsy at an outside institution are eligible as long as it is
                 confirmed that tumor specimens in paraffin blocks (preferred) or ≥ 25 unstained
                 slides, with an associated pathology report, are available.
    
              -  Female, Age ≥18 years (pre or postmenopausal).
    
              -  Signed informed consent
    
              -  Serum calcium or albumin-adjusted serum calcium ≥2.0mmol/L (8.0mg/dL) and ≤ 2.9
                 mmol/L (11.5mg/dL)
    
              -  Patients with reproductive potential must be willing to use, in combination with her
                 partner, 2 acceptable methods of effective contraception or practice sexual
                 abstinence throughout the study and continue for 5 months after study duration.
                 Subjects who are surgically sterile (eg, history of bilateral tubal ligation,
                 hysterectomy) or whose sexual partner is sterile (eg, history of vasectomy) are not
                 required to use additional contraceptive measures.
    
            Exclusion Criteria:
    
              -  Consideration for neoadjuvant therapy
    
              -  Serious infections including a history of active Hepatitis B, Hepatitis C or HIV
    
              -  Subject has known sensitivity to any of the products to be administered during the
                 study (e.g.., mammalian derived products, calcium, or vitamin D)
    
              -  Subject is pregnant or breast feeding, or planning to become pregnant/breastfeed
                 while on study through 5 months after the end of treatment
    
              -  Patients have prior history or current evidence of osteonecrosis or osteomyelitis of
                 the jaw, evidence of untreated local gum or oral infection, or non-healed dental or
                 oral surgery
    
              -  Patients with active dental or jaw conditions which require oral surgery/dental
                 procedures, including tooth extraction for the course of the study
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Pharmacodynamic markers of RANKL inhibition determination
    Time Frame:Change from baseline RANKL inhibition determination at one month
    Safety Issue:
    Description:Immunohistochemical analyses (IHC) of RANK and RANKL protein expression will be performed by Clarient Diagnostics Services Inc., Aliso Viejo, CA using prototype assays developed and optimized by Dako on their automated staining platform

    Secondary Outcome Measures

    Measure:Frequency of RANK and RANKL protein expression (by IHC) in operable breast cancer using Immunohistochemical analyses (IHC)
    Time Frame:Change from baseline frequency of RANK and RANKL protein expression at one month
    Safety Issue:
    Description:Immunohistochemical analyses (IHC) of RANK and RANKL protein expression will be performed by Clarient Diagnostics Services Inc., Aliso Viejo, CA using prototype assays developed and optimized by Dako on their automated staining platform

    Details

    Phase:Early Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:New York University School of Medicine

    Trial Keywords

    • RANK
    • RANKL

    Last Updated

    March 2, 2017