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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00450879
First received: March 20, 2007
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

This pilot trial studies how well pazopanib works in treating patients with newly diagnosed or locally and/or regionally recurrent breast cancer that can be removed by surgery. Pazopanib 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 to the tumor. Giving pazopanib before surgery may make the tumor smaller and reduce the amount of tissue that needs to be removed.


Condition Intervention
Male Breast Cancer
Recurrent Breast Cancer
Stage IA Breast Cancer
Stage IB Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Drug: pazopanib hydrochloride

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of GW786034 (Pazopanib), a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Operable Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response to GW786034 defined as change in molecular parameters such as phosphorylated VEGFR-2, microvessel density, tumor proliferation (Ki67), and apoptosis [ Time Frame: Baseline to 4 years ] [ Designated as safety issue: No ]
    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. We will adjust for multiple comparisons 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.


Enrollment: 40
Study Start Date: January 2007
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Patients receive pazopanib hydrochloride orally (PO) once daily for 12-20 days. Patients then undergo surgical resection of tumor between days 13 and 21 (24 hours after completion of pazopanib hydrochloride).
Drug: pazopanib hydrochloride
Given orally
Other Names:
  • GW786034B
  • Votrient

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the biologic effect of pazopanib hydrochloride, in terms of decreased phosphorylation of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2) and/or decreased microvessel density, in patients with newly diagnosed or locally and/or regionally recurrent operable breast cancer.

II. Determine the mechanism of antitumor effect of this drug, in terms of reduced tumor cell proliferation (Ki67) or increased apoptosis, in these patients.

SECONDARY OBJECTIVES:

I. Determine the change in levels of tissue VEGF in patients treated with this drug.

II. Determine the change in phosphorylation of epidermal growth factor receptor (EGFR), MAPK, and AKT in patients treated with this drug.

III. Evaluate gene expression patterns in patients treated with this drug. IV. Evaluate the change in VEGF and VEGFR-2 as circulating biomarkers in patients treated with this drug.

V. Evaluate the changes in circulating tumor cells in patients treated with this drug.

VI. Determine if steady-state plasma concentration of this drug correlates with inhibition of phospho-VEGFR-2.

VII. Evaluate the change in vascular permeability by bilateral dynamic contrast-enhanced MRI (DCE-MRI) of the breast in patients treated with this drug.

VIII. Compare DCE-MRI imaging of the tumor vasculature in the breast before, during, and after treatment with this drug.

OUTLINE: This is an open-label, pilot study.

Patients receive pazopanib hydrochloride orally (PO) once daily for 12-20 days. Patients then undergo surgical resection of tumor between days 13 and 21 (24 hours after completion of pazopanib hydrochloride).

Blood samples are collected periodically for analysis of circulating tumor cells and pharmacokinetic studies. Patients also undergo tumor biopsy at the time of surgery. Samples are analyzed by immunohistochemistry, microarray (gene expression profiling), and TUNEL assays to assess vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), epidermal growth factor receptor (EGFR), MAPK, AKT, phosphorylated (p) VEGFR-2, pEGFR, pMAPK, and pAKT activity, tumor cell proliferation (Ki67) and apoptosis, and microvessel density (using endothelial markers CD31 [PECAM-1], CD34, and CD 133).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of invasive adenocarcinoma of the breast by core needle biopsy or limited incisional biopsy
  • Tumor size >= 1.0 cm as assessed by physical exam or radiographic exam
  • Patients with histologically verified local and/or regional recurrence of invasive breast cancer that is amenable to surgery and meet all eligibility criteria may participate
  • No prior chemotherapy or hormonal therapy for this primary breast cancer
  • Patients who can undergo surgical treatment with either lumpectomy or mastectomy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • White blood cell (WBC) >= 3,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) and alanine aminotranferease (ALT) =< 2.5 times upper limit of normal (ULN)
  • Creatinine normal OR creatinine clearance >= 60 mL/min
  • Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) =< 1.2 times ULN
  • Urine protein:creatinine ratio =< 1
  • Patients must have blood pressure (BP) no greater than 140 mm Hg (systolic) and 90 mm Hg (diastolic) for eligibility; initiation or adjustment of BP medication is permitted prior to study entry provided that the average of three BP readings at a visit prior to enrollment is less than 140/90 mmHg
  • Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of GW786034 (pazopanib) will be determined following review by principal investigator
  • Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
  • Any concomitant medications that are associated with a risk of QTc prolongation and/or Torsades de Pointes should be discontinued or replaced with drugs that do not carry these risks, if possible; patients who must take medications with a risk or possible risk of Torsades de Pointes should be watched carefully for symptoms of QTc prolongation, such as syncope

Exclusion Criteria:

  • Patients with locally advanced breast cancer who are not candidates for surgical resection at time of initial evaluation, including patients with:

    • Tumor of any size with direct extension to chest wall or skin (T4a-c)
    • Inflammatory breast cancer (T4d)
  • Patients with evidence of metastatic disease
  • Patients may not be receiving any other investigational agents
  • Patients with history of allergic reactions attributed to compounds of similar chemical or biologic composition to GW786034 or other agents used in the study
  • Patients with any of the following conditions are excluded:

    • Serious or non-healing wound, ulcer, or bone fracture
    • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment
    • Any history of cerebrovascular accident (CVA) within the last 6 months
    • Current use of therapeutic warfarin. Note: Low molecular weight heparin and prophylactic low-dose warfarin are permitted; PT/PTT must meet the inclusion criteria (Section 5.1.8)
    • History of myocardial infarction, cardiac arrhythmia, admission for unstable angina, cardiac angioplasty or stenting within the last 12 weeks
    • History of venous thrombosis in last 12 weeks
    • Class III or IV heart failure as defined by the NYHA functional classification system (see Appendix C); a patient who has a history of Class II heart failure and is asymptomatic on treatment may be considered eligible
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situation that would limit compliance with study requirements
  • Baseline QTc >= 480 msecs or other significant electrocardiogram (ECG) abnormalities
  • Patients taking certain medications that act through the CYP450 system
  • Patients with any condition that impairs their ability to swallow and retain GW786034
  • Human immunodeficiency virus (HIV)-positive patients
  • Patients who are unable or unwilling to sign a written informed consent document
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00450879

Locations
United States, New Jersey
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
Sponsors and Collaborators
Investigators
Principal Investigator: Antoinette Tan Rutgers Cancer Institute of New Jersey
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00450879     History of Changes
Other Study ID Numbers: NCI-2009-00183, NCI-2009-00183, CDR0000534258, 040607, 040607, 7529, U01CA132194
Study First Received: March 20, 2007
Last Updated: December 13, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Endothelial Growth Factors
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014