Pazopanib in Treating Patients With Malignant Pleural Mesothelioma

Inclusion Criteria:

• 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
• ECOG performance status 0-2
• Life expectancy >= 12 weeks
• ANC >=1,500/mm^3
• Platelet count >= 100,000/mm^3
• WBC >= 3,000/mm^3
• 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

• 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 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 ancillary therapy considered investigational within the past 4 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
• No more than 1 prior systemic therapy for malignant pleural mesothelioma

• No major surgery (i.e., laparotomy) or open biopsy within the past 4 weeks

  • Insertion of a vascular access device is not considered major or minor surgery

• No minor surgery within the past 2 weeks

  • Insertion of a vascular access device is not considered major or minor surgery

• 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
• 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 other severe underlying disease that, in the judgment of the investigator, would limit study compliance