Clinical Trial: NCT02900469 - My Cancer Genome

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

URL:

https://clinicaltrials.gov/show/NCT02900469

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

Drug	Synonyms	Arms
denosumab	Xgeva	Denosumab & 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

Name	Type	Description	Interventions
Denosumab & surgery	Experimental	denosumab: 120 mg subcutaneous injection Surgery: 2-4 weeks after denosumab	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:	Completed
Lead Sponsor:	NYU Langone Health

Trial Keywords

RANK
RANKL

Last Updated

August 21, 2020

Clinical Trials /

Presurgical Trial of Denosumab in Breast Cancer