Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

This study is currently recruiting participants.
Verified February 2014 by City of Hope Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01409811
First received: August 3, 2011
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

This pilot clinical trial studies biomarkers in tissue samples from patients with newly diagnosed breast cancer treated with zoledronic acid (ZA). Studying samples of tumor tissue in the laboratory from patients receiving ZA may help doctors learn more about the effects of ZA on cells. It may also help doctors understand how well patients respond to treatment.


Condition Intervention
Estrogen Receptor-negative Breast Cancer
Estrogen Receptor-positive Breast Cancer
Invasive Ductal Breast Carcinoma
Progesterone Receptor-negative Breast Cancer
Progesterone Receptor-positive Breast Cancer
Stage IA Breast Cancer
Stage IB Breast Cancer
Stage II Breast Cancer
Drug: zoledronic acid
Other: laboratory biomarker analysis
Procedure: therapeutic conventional surgery

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of the Impact of a Single Dose of Zoledronic Acid on Biomarkers in Breast Cancer

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Changes in biomarkers of tumor growth and metastasis in women with newly diagnosed ER and/or PR positive invasive ductal breast cancer receiving zoledronic acid [ Time Frame: From baseline to the time of definitive surgery (day 10-14) ] [ Designated as safety issue: No ]
    We have identified 14 tumor biomarkers as primary endpoints and will control the false discover rate (FDR) among these by applying the sequential Bonferroni-type multiple testing procedure of Benjamini and Hochberg (1995).


Secondary Outcome Measures:
  • Changes in immunologic function after a single dose of zoledronic acid [ Time Frame: From baseline to the time of definitive surgery (day 10-14) ] [ Designated as safety issue: No ]
    We will apply the FDR-controlling procedure to immunological markers as one family. If change-in-endpoint data are not normally distributed, they will be transformed as appropriate.

  • Changes in the expression of tumor markers important to breast cancer progression and metastasis in women receiving zoledronic acid [ Time Frame: From baseline to the time of definitive surgery (day 10-14) ] [ Designated as safety issue: No ]
    We will apply the FDR-controlling procedure to tumor markers assessed by immunohistochemistry as one family. If change-in-endpoint data are not normally distributed, they will be transformed as appropriate.


Estimated Enrollment: 40
Study Start Date: September 2012
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (zoledronic acid)
Patients receive zoledronic acid IV over 15 minutes on day 1. Patients then undergo planned definitive surgery (lumpectomy or mastectomy) on day 10-14. Tissue samples from the initial biopsy and definitive surgery are collected to measure changes in biomarkers of tumor growth and metastasis, immunologic function, and the expression of genes important to breast cancer progression and metastasis.
Drug: zoledronic acid
Given IV
Other Names:
  • CGP 42446
  • CGP42446A
  • NDC-zoledronate
  • zoledronate
  • Zometa
Other: laboratory biomarker analysis
Correlative studies
Procedure: therapeutic conventional surgery
Undergo definitive lumpectomy or mastectomy

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate 14 tumor biomarkers of growth and metastasis (10 by microarray and 4 by RT-PCR) for change in response to ZA.

SECONDARY OBJECTIVES:

I. To evaluate 30 measures of immunologic function (by Luminex panel) for change in response to ZA a) after 48-72 hours and b) after 10-14 days.

II. To explore additional tumors biomarkers (approximately 20 by immunohistochemistry) for change in response to ZA.

OUTLINE: Patients receive zoledronic acid intravenously (IV) over 15 minutes on day 1. Patients then undergo planned definitive surgery (lumpectomy or mastectomy) on day 10-14. Tissue samples from the initial biopsy and definitive surgery are collected to measure changes in biomarkers of tumor growth and metastasis, immunologic function, and the expression of genes important to breast cancer progression and metastasis.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Postmenopausal women
  • Diagnosis of early stage, invasive ductal carcinoma (for which a lumpectomy or mastectomy is planned prior to systemic therapy)
  • Estrogen receptor (ER)/progesterone receptor (PR) positive tumor (as confirmed by City of Hope Pathology Department if done on the outside) or
  • Biopsy proven ER/PR positive tumor
  • Ability to provide informed consent

Exclusion Criteria:

  • Tumor that lacks both estrogen and progesterone receptors
  • Patients who will receive neoadjuvant therapy prior to definitive surgery
  • Bisphosphonate therapy currently or within the past 12 months
  • Regular use of anti-inflammatory agents, with the exception of a baby aspirin regimen per principal investigator's (PI's) discretion
  • Pregnancy
  • Renal impairment as determined by a creatinine clearance < 60 ml/min as calculated by the Cockroft-Gault formula using the patient's actual weight
  • Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures
  • Recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01409811

Locations
United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Joanne E. Mortimer, MD    800-826-4673    jmortimer@coh.org   
Principal Investigator: Joanne E. Mortimer, MD         
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Joanne Mortimer City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01409811     History of Changes
Other Study ID Numbers: 10192, NCI-2011-02137
Study First Received: August 3, 2011
Last Updated: February 10, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Carcinoma, Ductal, Breast
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Ductal
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014