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

Primary Purpose

Estrogen Receptor-positive Breast Cancer, Invasive Ductal Breast Carcinoma, Progesterone Receptor-positive Breast Cancer

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
zoledronic acid
laboratory biomarker analysis
therapeutic conventional surgery
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Estrogen Receptor-positive Breast Cancer

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

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
  • Renal impairment as determined by a creatinine clearance < 60 ml/min as calculated by the Cockcroft-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)

Sites / Locations

  • City of Hope Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (zoledronic acid)

Arm Description

Patients receive a single dose of zoledronic acid 4 mg IV over 15 minutes on day 1. Patients then undergo planned definitive surgery (lumpectomy or mastectomy) on day 10-23. Tissue and blood 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. zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies therapeutic conventional surgery: Undergo definitive lumpectomy or mastectomy

Outcomes

Primary Outcome Measures

Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline
After the trial's premature closure, no data were collected for the primary endpoints; however, data on 14 of 30 secondary endpoints were obtained and are summarized below. Serum level (pg/mL) per biomarker was log-transformed. Change from baseline over time was evaluated using a generalized linear mixed model where follow-up time was represented by terms for the sequence of post-baseline samples or for (log)day on study. To recognize regression to the mean across repeated samples, a term for biomarker level at baseline, with or without interaction by time, was included when it improved the model's fit to the observed data. With 14 biomarkers sampled twice after baseline, there were 28 evaluations of change in biomarker level with exposure to study drug. Therefore, to control the False Discovery Rate (FDR), only evaluations that maintained the study's FDR at no more than 5 percent were accepted as true.

Secondary Outcome Measures

Full Information

First Posted
August 3, 2011
Last Updated
April 28, 2020
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01409811
Brief Title
Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid
Official Title
A Pilot Study of the Impact of a Single Dose of Zoledronic Acid on Biomarkers in Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Terminated
Why Stopped
Study closed after it became too difficult to interest patients in participating.
Study Start Date
September 14, 2012 (undefined)
Primary Completion Date
January 1, 2015 (Actual)
Study Completion Date
February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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 10-23 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 10-23. Tissue and blood 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. After completion of study treatment, patients are followed up at 40-44 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Estrogen Receptor-positive Breast Cancer, Invasive Ductal Breast Carcinoma, Progesterone Receptor-positive Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage IIA Breast Cancer, Stage IIB Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (zoledronic acid)
Arm Type
Experimental
Arm Description
Patients receive a single dose of zoledronic acid 4 mg IV over 15 minutes on day 1. Patients then undergo planned definitive surgery (lumpectomy or mastectomy) on day 10-23. Tissue and blood 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. zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies therapeutic conventional surgery: Undergo definitive lumpectomy or mastectomy
Intervention Type
Drug
Intervention Name(s)
zoledronic acid
Other Intervention Name(s)
CGP 42446, CGP42446A, NDC-zoledronate, zoledronate, Zometa
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Procedure
Intervention Name(s)
therapeutic conventional surgery
Intervention Description
Undergo definitive lumpectomy or mastectomy
Primary Outcome Measure Information:
Title
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline
Description
After the trial's premature closure, no data were collected for the primary endpoints; however, data on 14 of 30 secondary endpoints were obtained and are summarized below. Serum level (pg/mL) per biomarker was log-transformed. Change from baseline over time was evaluated using a generalized linear mixed model where follow-up time was represented by terms for the sequence of post-baseline samples or for (log)day on study. To recognize regression to the mean across repeated samples, a term for biomarker level at baseline, with or without interaction by time, was included when it improved the model's fit to the observed data. With 14 biomarkers sampled twice after baseline, there were 28 evaluations of change in biomarker level with exposure to study drug. Therefore, to control the False Discovery Rate (FDR), only evaluations that maintained the study's FDR at no more than 5 percent were accepted as true.
Time Frame
"48-72 hrs" and "Surgery (10-23 days)"

10. Eligibility

Sex
Female
Accepts Healthy Volunteers
No
Eligibility 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 Renal impairment as determined by a creatinine clearance < 60 ml/min as calculated by the Cockcroft-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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joanne Mortimer
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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