Pazopanib in Treating Patients With Recurrent or Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00509587
First received: July 30, 2007
Last updated: April 1, 2014
Last verified: April 2013
  Purpose

This phase II trial is studying how well giving pazopanib works in treating patients with recurrent or metastatic invasive breast cancer. Pazopanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.


Condition Intervention Phase
Male Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Drug: pazopanib hydrochloride
Procedure: pharmacological study
Procedure: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of GW786034 (Pazopanib) in Patients With Recurrent and/or Metastatic Invasive Breast Carcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Antitumor activity, in terms of objective response rates (partial and complete responses) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Summarized using summary statistics, such as the mean, median, counts and proportion.


Secondary Outcome Measures:
  • Duration of objective response [ Time Frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Duration of stable disease [ Time Frame: From the start of the treatment until the criteria for progression are met, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Computed using the Kaplan-Meier method.

  • Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Computed using the Kaplan-Meier method.

  • Adverse events graded according to the NCI CTCAE version 3.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 21
Study Start Date: June 2007
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pazopanib hydrochloride)
Patients receive oral pazopanib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: pazopanib hydrochloride
Given orally
Other Names:
  • GW786034B
  • Votrient
Procedure: pharmacological study
Correlative studies
Other Name: pharmacological studies
Procedure: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVE:

I. To determine the antitumor activity of pazopanib, in terms of objective response rate (partial and complete response), in patients with recurrent or metastatic invasive breast cancer.

SECONDARY OBJECTIVES:

I. To determine the duration of objective response, rate and duration of stable disease.

II. To determine 6-month progression-free and median and overall survival rates in patients treated with this drug.

III. To document the safety and tolerability of this drug in these patients.

OUTLINE: This is a multicenter, open label study.

Patients receive oral pazopanib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and at 1, 4, and 8 weeks for correlative laboratory studies. Blood samples are evaluated for the following tumor markers by ELISA: VEGF, bFGF, sFLT-1, sTIE-2, sE-Selectin, VCAM-1, PDGF-AA, PDGF-AB and PDGF-BB. TSP-1 in plasma is measured by Accucyte™ competitive immunoassay.

After completion of study treatment, patients are followed every 3 months.

  Eligibility

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

Criteria:

  • No prior bevacizumab
  • Histologically or cytologically confirmed invasive breast carcinoma (recurrent or metastatic disease)
  • Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral CT scan
  • Patients who may still benefit from hormonal therapy are ineligible (patients with hormone receptor-positive breast cancer should have received appropriate sequential hormonal therapy for metastatic disease until disease progression)
  • Patients with HER-2 positive disease who have not yet received trastuzumab (Herceptin®) to maximal benefit are ineligible (patients with disease progression during trastuzumab therapy are eligible)
  • No known brain metastases
  • ECOG performance status (PS) 0-1 or Karnofsky PS 60-100%
  • Life expectancy > 12 weeks
  • Absolute neutrophil count >= 1,500/mm³
  • Platelets >=100,000/mm³
  • Total bilirubin normal (exception made for patients with known Gilbert's disease)
  • AST/ALT =< 2.5 times upper limit of normal (ULN)
  • No proteinuria > +1 on two consecutive dipsticks taken >= 1 week apart
  • PT/INR/PTT =< 1.2 times ULN
  • No allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib or other study agents
  • No QTc prolongation (defined as a QTc interval >= 500 msecs) or other significant ECG abnormalities
  • No condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, or active peptic ulcer disease) that would impair ability to swallow and retain study drug
  • No poorly controlled hypertension (systolic blood pressure [BP] >= 140 mm Hg or diastolic BP >= 90 mm Hg) Initiation or adjustment of BP medication is allowed prior to study entry provided that the average of 3 BP readings prior to study entry is < 140/90 mm Hg
  • No serious or non-healing wound, ulcer, or bone fracture
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the last 4 weeks
  • No cerebrovascular accident within the last 6 months
  • No myocardial infarction, cardiac arrhythmia, hospital admission for unstable angina within the last 12 weeks
  • No venous thrombosis within the last 12 weeks
  • No NYHA class III-IV heart failure Patients with a history of class II heart failure may be considered eligible provided they are asymptomatic on treatment
  • No concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would preclude study compliance
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy, or surgery
  • No cardiac angioplasty or stenting within the last 12 weeks
  • No more than 1 prior chemotherapy regimen for recurrent disease
  • No prior surgical procedures affecting absorption
  • No CYP2C9 substrates during or for 1-2 weeks after completion of study treatment, including any of the following:

Therapeutic warfarin Low molecular weight heparin or prophylactic low-dose warfarin are allowed

  • No CYP2C9 substrates during or for 1-2 weeks after completion of study treatment, including any of the following:

    • Erectile dysfunction agents: sildenafil, tadalafil, or vardenafil
    • Antiarrhythmics: bepridil, flecainide, lidocaine, mexilitine, amiodarone, or quinidine
    • Immune modulators: cyclosporine, tacrolimus, or sirolimus
    • Miscellaneous: theophylline, quetiapine, or risperidone
  • No CYP2C9 substrates during or for 1-2 weeks after completion of study treatment, including any of the following:

    • Oral hypoglycemics: glipizide, glyburide, or tolbutamide
    • Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, or methylergonovine
    • Neuroleptics: pimozide
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy
  • WBC >= 3,000/mm³
  • No more than 2 prior palliative systemic chemotherapy regimens for de novo metastatic disease
  • Creatinine normal OR creatinine clearance >= 60 mL/min
  • At least 3 months since prior trastuzumab
  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: NCT00509587

Locations
Canada, British Columbia
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
The Ottawa Hospital Cancer Centre (Ottawa Health Research Institute) Civic Campus
Ottawa, Ontario, Canada, K1Y 4E9
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Investigators
Principal Investigator: Natasha Leighl University Health Network-Princess Margaret Hospital
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00509587     History of Changes
Other Study ID Numbers: NCI-2009-00199, NCI-2009-00199, CDR0000557347, PHL-057, PHL-057, 7638, N01CM62203
Study First Received: July 30, 2007
Last Updated: April 1, 2014
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

ClinicalTrials.gov processed this record on August 28, 2014