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Trial record 12 of 621 for:    surgery | Recruiting, Not yet recruiting Studies | Interventional Studies | Breast Cancer

Presurgical Trial of Denosumab in Breast Cancer

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ClinicalTrials.gov Identifier: NCT02900469
Recruitment Status : Recruiting
First Posted : September 14, 2016
Last Update Posted : September 26, 2019
Sponsor:
Information provided by (Responsible Party):
NYU Langone Health

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: denosumab Procedure: Surgery Early Phase 1

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.


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Study Type : Interventional
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pre-surgical Evaluation of Denosumab in Patients With Operable Invasive Breast Cancer
Study Start Date : October 2016
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Denosumab

Arm Intervention/treatment
Experimental: Denosumab & surgery

denosumab: 120 mg subcutaneous injection

Surgery: 2-4 weeks after denosumab

Biological: denosumab
denosumab: 120 mg subcutaneous injection
Other Name: Xgeva

Procedure: Surgery
Surgery: approximately 2-4 weeks after dosing of denosumab




Primary Outcome Measures :
  1. Pharmacodynamic markers of RANKL inhibition determination [ Time Frame: Change from baseline RANKL inhibition determination at one month ]
    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 :
  1. 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 ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02900469


Contacts
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Contact: Sylvia Adams, MD (212) 263-5795 sylvia.adams@nyumc.org

Locations
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United States, New York
NYU Perlmutter Cancer Center Recruiting
New York, New York, United States, 10016
Contact: Sylvia Adams, MD       sylvia.adams@nyumc.org   
Principal Investigator: Sylvia Adams, MD         
Sub-Investigator: Francisco Esteva, MD, PhD         
Sub-Investigator: James Speyer, MD         
Sub-Investigator: Yelena Novik, MD         
Sub-Investigator: Ruth Oratz, MD         
Sub-Investigator: Deborah Axelrod, MD         
Sub-Investigator: Amber Guth, MD         
Sub-Investigator: Karen Hiotis, MD         
Sub-Investigator: Freya Schnabel, MD         
Sub-Investigator: Richard Shapiro, MD         
Sub-Investigator: Daniel Roses, MD         
Sub-Investigator: Maryann Kwa, MD         
Sub-Investigator: Franco Muggia, MD         
Sponsors and Collaborators
NYU Langone Health
Investigators
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Principal Investigator: Sylvia Adams, MD NYU Perlmutter Cancer Center

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Responsible Party: NYU Langone Health
ClinicalTrials.gov Identifier: NCT02900469     History of Changes
Other Study ID Numbers: s14-01311
First Posted: September 14, 2016    Key Record Dates
Last Update Posted: September 26, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by NYU Langone Health:
RANK
RANKL
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Denosumab
Bone Density Conservation Agents
Physiological Effects of Drugs