Pazopanib in Treating Patients With Newly Diagnosed or Locally and/or Regionally Recurrent Breast Cancer That Can Be Removed By Surgery
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|ClinicalTrials.gov Identifier: NCT00450879|
Recruitment Status : Terminated
First Posted : March 22, 2007
Last Update Posted : March 25, 2015
|Condition or disease||Intervention/treatment||Phase|
|Male Breast Carcinoma Recurrent Breast Carcinoma Stage IA Breast Cancer Stage IB Breast Cancer Stage IIA Breast Cancer Stage IIB Breast Cancer Stage IIIA Breast Cancer||Drug: Pazopanib Hydrochloride Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging Other: Pharmacological Study Other: Laboratory Biomarker Analysis||Phase 1|
I. To determine the biologic effect, measured by a decrease in phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR-2) and/or decrease in microvessel density, in breast tumor biopsies after treatment with daily oral GW786034 (pazopanib hydrochloride) for at least 12 consecutive days in early stage, operable breast cancer or local and/or regional recurrence that is amenable to surgery.
II. To determine the mechanism of antitumor effect, measured by a reduction in tumor cell proliferation (Ki67) or an increase in apoptosis in breast tumor biopsies after treatment with GW786034.
I. To determine the change in levels of tissue vascular endothelial growth factor (VEGF) in breast tumor biopsies after treatment with GW786034.
II. To evaluate the change in phosphorylation of epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), and protein kinase B (AKT) in breast tumor biopsies after treatment with GW786034.
III. To identify gene expression patterns in breast tumor biopsies before and after treatment with GW786034.
IV. To evaluate the change in VEGF (in the plasma) and VEGFR-2 (in the serum) as circulating biomarkers after treatment with GW786034.
V. To evaluate the change in circulating tumor cells in peripheral blood after treatment with GW786034.
VI. To determine whether the steady-state plasma concentration of GW786034 correlates with inhibition of phosphorylated (phospho)-VEGFR-2 and other endpoints in breast tumor biopsies.
VII. To evaluate the change in vascular permeability by dynamic contrast enhanced (DCE)-magnetic resonance imaging (MRI) of the breast after treatment with GW786034.
VIII. To compare the images obtained with bilateral DCE-MRI of the breast before, during, and after treatment with GW786034.
Patients receive pazopanib hydrochloride orally (PO) once daily (QD) for 12-20 days in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection of tumor between days 13 and 21 (24 hours after completion of pazopanib hydrochloride).
After completion of study treatment, patients are followed up within 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of GW786034 (Pazopanib), a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Operable Breast Cancer|
|Study Start Date :||January 2007|
|Actual Primary Completion Date :||November 2010|
|Actual Study Completion Date :||September 2011|
U.S. FDA Resources
Experimental: Treatment (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride PO QD for 12-20 days in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection of tumor between days 13 and 21 (24 hours after completion of pazopanib hydrochloride).
Drug: Pazopanib Hydrochloride
Other Names:Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Other Names:Other: Pharmacological Study
Other Name: pharmacological studiesOther: Laboratory Biomarker Analysis
- Change in molecular parameters such as phosphorylated VEGFR-2, microvessel density, tumor proliferation (Ki67), and apoptosis [ Time Frame: Baseline to up to 20 days ]The pre-post comparison of the biologic effects in the tumor can be done by a paired t-test as they are all continuous variables. If the differences are not normally distributed, transformations or non-parametric methods will be applied. Multiple comparisons will be adjusted for using Bonferroni method as the biologic effects are measured by four variables. The relationship among these four variables will be analyzed using factor analysis to see if they can be reduced to one or two representative indices.
- Change in plasma VEGF levels [ Time Frame: Baseline to up to 20 days ]The pre-post difference of the tissue variables will be regressed on the plasma VEGF levels.
- Change in serum VEGFR-2 levels [ Time Frame: Baseline to up to 20 days ]The pre-post difference of the tissue variables will be regressed on the serum VEGFR-2 levels.
- Change in circulating tumor cells [ Time Frame: Baseline to up to 20 days ]
- Stead-state plasma concentration of pazopanib hydrochloride [ Time Frame: Baseline (pre-dose day 1), day 8, and 24-72 hours prior to surgery ]The pre-post difference of the tissue variables will be regressed on the plasma concentration of pazopanib hydrochloride.
- Change in images obtained with bilateral DCE-MRI of the breast [ Time Frame: Baseline to up to 20 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00450879
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08903|
|Principal Investigator:||Antoinette Tan||Rutgers Cancer Institute of New Jersey|