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Male Breast CarcinomaPhase 1NCT00450879

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

A Phase 1 study testing Pazopanib Hydrochloride, Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Pharmacological Study in people with Male Breast Carcinoma and Recurrent Breast Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pazopanib Hydrochloride, Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Pharmacological Study
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteUnited States
Study dates
Jan 2007to Sep 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 of 0, 1, or 2
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  • White blood cells (WBC) >= 3,000/uL
  • Platelets >= 100,000/uL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal (ULN)
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) =< 1.2 x institutional ULN
  • Urine protein:creatinine ratio (UPC) of less than or equal to 1 as assessed in a random or spot urine sample
  • Patients must have blood pressure (BP) no greater than 140 mmHg (systolic) and 90 mmHg (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 of their case by the Principal Investigator
  • Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should (barrier method of birth control; abstinence)
  • 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

Who cannot join

  • Patients with locally advanced breast cancer who are not candidates for surgical resection at time of initial evaluation, this may include patients with locally advanced disease such as:
  • 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
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW786034 (pazopanib) or other agents used in the study are excluded
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  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with a baseline QTc >= 480 msecs or other significant electrocardiogram (ECG) abnormalities are ineligible
  • Patients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher, or diastolic blood pressure of 90 mmHg or higher) are ineligible
  • Certain medications that act through the cytochrome p 450 (CYP450) system are specifically prohibited in patients receiving GW786034 (pazopanib); certain other agents should be used with caution
  • Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous [IV] alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain GW786034 (pazopanib) tablets are excluded
  • 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 * 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 New York Heart Association (NYHA) functional classification system; 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
  • Pregnant women are excluded from this study; procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain GW786034 (pazopanib) tablets are excluded
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Inability to understand or unwillingness to sign a written informed consent document

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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.

Being tested
Pazopanib Hydrochloride, Dynamic Contrast-Enhanced Magnetic Resonance Imaging, Pharmacological Study, Laboratory Biomarker Analysis
Medical subject headings
Breast Neoplasms, Male, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pazopanib HydrochlorideDrug

    Also called GW786034B, Votrient

    Given PO

  • Dynamic Contrast-Enhanced Magnetic Resonance ImagingProcedure or surgery

    Also called DCE MRI, DCE-MRI

    Correlative studies

  • Pharmacological StudyOther

    Also called pharmacological studies

    Correlative studies

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT00450879
Study groupRoleWhat they receive
Treatment (pazopanib hydrochloride)ExperimentalPatients 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).
Receives: Drug: Pazopanib Hydrochloride; Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in molecular parameters such as phosphorylated VEGFR-2, microvessel density, tumor proliferation (Ki67), and apoptosis

    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.

    Measured: Baseline to up to 20 days

Secondary outcomes (5)

  1. Change in plasma VEGF levels

    The pre-post difference of the tissue variables will be regressed on the plasma VEGF levels.

    Measured: Baseline to up to 20 days

  2. Change in serum VEGFR-2 levels

    The pre-post difference of the tissue variables will be regressed on the serum VEGFR-2 levels.

    Measured: Baseline to up to 20 days

  3. Change in circulating tumor cells

    Measured: Baseline to up to 20 days

  4. Stead-state plasma concentration of pazopanib hydrochloride

    The pre-post difference of the tissue variables will be regressed on the plasma concentration of pazopanib hydrochloride.

    Measured: Baseline (pre-dose day 1), day 8, and 24-72 hours prior to surgery

  5. Change in images obtained with bilateral DCE-MRI of the breast

    Measured: Baseline to up to 20 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2007 (estimated)
  2. Study startJan 2007
  3. Primary completionNov 2010
  4. Study completionSep 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00450879
Sponsor's protocol ID
NCI-2009-00183
Other IDs
NCI-2009-00183, CDR0000534258, 040607, 040607, 7529, U01CA132194, P30CA072720
Status last verified
Jun 2013
First submitted
20 Mar 2007
Last updated
25 Mar 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pazopanib Hydrochloride, Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Pharmacological Study in people with Male Breast Carcinoma and Recurrent Breast Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in molecular parameters such as phosphorylated VEGFR-2, microvessel density, tumor proliferation (Ki67), and apoptosis (time frame: Baseline to up to 20 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00450879.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2015.

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