• Proportion of patients who are progression-free at 6 months [ Designated as safety issue: No ]
  

• Response to treatment [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  
• Progression-free survival [ Designated as safety issue: No ]
  
• Duration of response [ Designated as safety issue: No ]
  
• Time to treatment failure [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  
• Tumor markers of angiogenesis [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the effect of pazopanib hydrochloride on the proportion of patients with malignant pleural mesothelioma who are progression-free at 6 months based on the RECIST criteria.
• Determine the clinical toxicities of this drug in this patient population.

Secondary

• Determine the objective tumor response status in these patients as measured by the RECIST criteria or the modified RECIST criteria.
• Determine the response rate in patients treated with this drug.
• Determine the effect of this drug on overall survival and time to progression in these patients.
• Assess predictive markers of activity of this drug in these patients.
• Assess serologic markers of target inhibition by this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral pazopanib hydrochloride once daily on days 1-21. Treatment repeats every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.

Blood is collected at baseline and prior to each course of therapy and analyzed for markers of angiogenesis.

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

PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignant pleural mesothelioma

  • Measurable disease
  • No progressive disease inside or outside of any prior radiation field

• No symptomatic, untreated, or uncontrolled CNS metastases

  • Patients with CNS metastases treated with whole brain radiation (WBRT) may be enrolled after completion of WBRT

    • Patients may begin study therapy as early as the next day after completion of WBRT

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• ANC ≥1,500/mm³
• Platelet count ≥ 100,000/mm³
• WBC ≥ 3,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 50 mL/min
• Proteinuria ≤ 1+ on 2 consecutive dipsticks taken ≥ 1 week apart
• PT/INR/PTT ≤ 1.2 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective nonhormonal contraception
• No uncontrolled infection
• No uncontrolled blood pressure (BP) (defined as systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg in spite of adequate anti-hypertensive therapy)

• No condition that impairs ability to swallow and retain study drug tablets including, but not limited to, any of the following:

  • Gastrointestinal tract disease resulting in an inability to take oral medication
  • Requirement for IV alimentation
  • Prior surgical procedures affecting absorption
  • Active peptic ulcer disease
• No other severe underlying disease that, in the judgment of the investigator, would limit study compliance

• No other primary malignancy except for carcinoma in situ of the cervix or nonmelanomatous skin cancer, unless that prior malignancy was diagnosed and definitively treated ≥ 5 years ago with no subsequent evidence of recurrence

  • Patients with a history of low-grade (Gleason score ≤ 6) localized prostate cancer are eligible even if diagnosed within the past 5 years
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or other agents used in the study

• None of the following concurrent severe and/or uncontrolled medical conditions:

  • Serious or nonhealing wound, ulcer, or bone fracture
  • Abdominal fistula, diverticulosis, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • Poorly controlled diabetes
  • Interstitial pneumonia
  • Extensive and symptomatic interstitial fibrosis of the lung

• No cardiovascular illness or complication, including any of the following:

  • Any history of cerebrovascular accident within the past 6 months
  • History of myocardial infarction (prior electrocardiographic evidence of myocardial injury)
  • History of cardiac arrhythmia (prior electrocardiographic evidence of abnormal heart rhythm)
  • Admission for unstable angina
  • Cardiac angioplasty or stenting within the past 12 months

  • NYHA class III-IV heart failure

    • Asymptomatic NYHA class II heart failure allowed
  • QTc prolongation (defined as a QTc interval ≥ 500 msecs) or other significant electrocardiogram abnormalities
  • Venous thrombosis within the past 12 weeks
• No symptomatic, untreated, or uncontrolled seizure disorder
• No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit study compliance
• No significant traumatic injury within the past 4 weeks

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No more than 1 prior systemic therapy for malignant pleural mesothelioma
• No ancillary therapy considered investigational within the past 4 weeks
• No major surgery (i.e., laparotomy) or open biopsy within the past 4 weeks*
• No minor surgery within the past 2 weeks*

• Prior palliative radiotherapy allowed

  • No prior palliative radiotherapy to the chest except for a maximum of 3 fractions of radiotherapy for superior vena cava syndrome

• No concurrent therapeutic warfarin

  • Low molecular-weight heparin or prophylactic low-dose warfarin allowed
• No other concurrent chemotherapy, immunotherapy, hormonal therapy, or radiotherapy
• No concurrent medications that act through the CYP450 system
• No concurrent combination antiretroviral therapy for HIV-positive patients NOTE: *Insertion of a vascular access device is not considered major or minor surgery