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Trial record 2 of 22 for:    denosumab AND breast cancer

Presurgical Trial of Denosumab in Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by New York University School of Medicine
Sponsor:
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT02900469
First received: August 29, 2016
Last updated: November 17, 2016
Last verified: November 2016
  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.

Condition Intervention Phase
Breast Cancer
Biological: denosumab
Procedure: Surgery
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pre-surgical Evaluation of Denosumab in Patients With Operable Invasive Breast Cancer

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Pharmacodynamic markers of RANKL inhibition determination [ Time Frame: Change from baseline RANKL inhibition determination at one month ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 35
Study Start Date: October 2016
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02900469

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

Locations
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
New York University School of Medicine
Investigators
Principal Investigator: Sylvia Adams, MD NYU Perlmutter Cancer Center
  More Information

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT02900469     History of Changes
Other Study ID Numbers: s14-01311 
Study First Received: August 29, 2016
Last Updated: November 17, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
RANK
RANKL

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Denosumab
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 02, 2016