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
Conditions
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.
Interventions
DRUGzoledronic acid
Given IV
OTHERlaboratory biomarker analysis
Correlative studies
PROCEDUREtherapeutic conventional surgery
Undergo definitive lumpectomy or mastectomy
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | 48-72 hrs and Surgery (10-23 days) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Zoledronic Acid) 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 | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Insurance denial | 1 |
Baseline characteristics
| Characteristic | Treatment (Zoledronic Acid) |
|---|---|
| Age, Continuous | 61 years |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 6 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 8 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
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.
Time frame: 48-72 hrs and Surgery (10-23 days)
Population: The analysis included data from all evaluable subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | MIG @ Surgery (Day 10-23) | 0.62 (log)pg/mL | Standard Error 0.14 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | IL-12 @ 48-72 hrs | 0.23 (log)pg/mL | Standard Error 0.06 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | IL-12 @ Surgery (Day 10-23) | -0.01 (log)pg/mL | Standard Error 0.05 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | IP-10 @ Surgery (Day 10-23) | 0.16 (log)pg/mL | Standard Error 0.08 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | MIG @ 48-72 hrs | 2.31 (log)pg/mL | Standard Error 0.24 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | IP-10 @ 48-72 hrs | 1.47 (log)pg/mL | Standard Error 0.18 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | IFN-gamma @ Surgery (Day 10-23) | -0.01 (log)pg/mL | Standard Error 0.02 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | Eotaxin @ 48-72 hrs | -0.23 (log)pg/mL | Standard Error 0.06 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | Eotaxin @ Surgery (Day 10-23) | 0.02 (log)pg/mL | Standard Error 0.06 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | MIP1B @ 48-72 hrs | 0.37 (log)pg/mL | Standard Error 0.17 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | MIP1B @ Surgery (Day 10-23) | 0.28 (log)pg/mL | Standard Error 0.25 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | EGF @ 48-72 hrs | -0.18 (log)pg/mL | Standard Error 0.1 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | EGF @ Surgery (Day 10-23) | 0.25 (log)pg/mL | Standard Error 0.12 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | MCP-1 @ 48-72 hrs | 0.15 (log)pg/mL | Standard Error 0.08 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | MCP-1 @ Surgery (Day 10-23) | -0.02 (log)pg/mL | Standard Error 0.08 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | IFN-alpha per (log)Day until Surgery (Day 10-23) | -0.026 (log)pg/mL | Standard Error 0 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | MIP1A per (log)Day until Surgery (Day 10-23) | 0.12 (log)pg/mL | Standard Error 0.05 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | IL-2R @ 48-72 hrs | 0.17 (log)pg/mL | Standard Error 0.04 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | IL-2R @ Surgery (Day 10-23) | 0.10 (log)pg/mL | Standard Error 0.11 |
| Treatment (Zoledronic Acid) | Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline | IFN-gamma @ 48-72 hrs | 0.04 (log)pg/mL | Standard Error 0.01 |