Pazopanib in Treating Patients With Recurrent or Metastatic Breast Cancer
Condition: Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms; Recurrence
Intervention: pazopanib hydrochloride; pharmacological study; laboratory biomarker analysis
Intervention description: Given orally; Correlative studies; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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