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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01409811
First received: August 3, 2011
Last updated: July 17, 2014
Last verified: July 2014

August 3, 2011
July 17, 2014
September 2012
December 2015   (final data collection date for primary outcome measure)
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).
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 21-24) ] [ Designated as safety issue: No ]
We will investigate the use of Bayesian rank ensemble estimates to determine the top ten biomarkers based on rank by change in mean serum value pre- to post-treatment with zoledronic acid to avoid multiple testing. Descriptive statistics will be provided for each biomarker (both serum and tumor) pre- and post-treatment with zoledronic acid. Rates and associated confidence intervals will be provided for categorical data variables and means, medians, percentiles, and 95% confidence limits will be provided for continuous data variables.
Complete list of historical versions of study NCT01409811 on ClinicalTrials.gov Archive Site
  • 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.
  • Changes in immunologic function after a single dose of zoledronic acid [ Time Frame: At baseline, 48-72 hours after zoledronic acid, and at the time of definitive surgery (21-24 days) ] [ Designated as safety issue: No ]
  • Changes in the expression of genes important to breast cancer progression and metastasis in women receiving zoledronic acid [ Time Frame: From baseline to the time of definitive surgery (21-24 days) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid
A Pilot Study of the Impact of a Single Dose of Zoledronic Acid on Biomarkers in Breast Cancer

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.

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.

Interventional
Not Provided
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    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
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.
Interventions:
  • Drug: zoledronic acid
  • Other: laboratory biomarker analysis
  • Procedure: therapeutic conventional surgery
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
40
Not Provided
December 2015   (final data collection date for primary outcome measure)

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)
Female
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01409811
10192, NCI-2011-02137
Yes
City of Hope Medical Center
City of Hope Medical Center
National Cancer Institute (NCI)
Principal Investigator: Joanne Mortimer City of Hope Medical Center
City of Hope Medical Center
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP