Pazopanib in Treating Patients With Newly Diagnosed or Locally and/or Regionally Recurrent Breast Cancer That Can Be Removed By Surgery

Stage IIIA Breast Cancer Clinical Trial

Official title: Pilot Study of GW786034 (Pazopanib), a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Operable Breast Cancer

Status Terminated

Clinical Trial Summary

This pilot clinical trial studies how well pazopanib hydrochloride works in treating patients with breast cancer that is newly diagnosed or has come back at or near the same place as the original tumor and can be removed by surgery. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by preventing the growth of new blood vessels necessary for tumor growth. Giving pazopanib hydrochloride before surgery may make the tumor smaller and reduce the amount of tissue that needs to be removed.

Clinical Trial Description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

OUTLINE:

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Neoplasms, Male
• Carcinoma
• 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

• NCT number: NCT00450879
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Terminated
• Phase: Phase 1
• Start date: January 2007
• Completion date: September 2011