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

NCT00450879 | Terminated Phase 1

• 6 other identifiers: NCI-2009-00183CDR00005342580406077529U01CA132194P30CA072720
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (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.

  Baseline to up to 20 days

Secondary Outcomes (5)

• Change in plasma VEGF levels

  Baseline to up to 20 days

• Change in serum VEGFR-2 levels

  Baseline to up to 20 days

• Change in circulating tumor cells

  Baseline to up to 20 days

• Stead-state plasma concentration of pazopanib hydrochloride

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

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

  Baseline to up to 20 days

Study Arms (1)

Treatment (pazopanib hydrochloride)

EXPERIMENTAL

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; Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis

Interventions

Pazopanib Hydrochloride DRUG

Given PO

Also known as: GW786034B, Votrient

Treatment (pazopanib hydrochloride)

Dynamic Contrast-Enhanced Magnetic Resonance Imaging PROCEDURE

Correlative studies

Also known as: DCE MRI, DCE-MRI

Treatment (pazopanib hydrochloride)

Pharmacological Study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (pazopanib hydrochloride)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pazopanib hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Antoinette Tan

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2007
• First Posted: March 22, 2007
• Study Start: January 1, 2007
• Primary Completion: November 1, 2010
• Study Completion: September 1, 2011
• Last Updated: March 25, 2015

Record last verified: 2013-06

Locations

US (1)