This phase II trial is study how well AZD2171 works in treating patients with malignant pleural mesothelioma that cannot be removed by surgery. AZD2171 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

PRIMARY OBJECTIVES:

I. Determine the objective confirmed, complete, and partial response rates in patients with unresectable malignant pleural mesothelioma treated with AZD2171.

SECONDARY OBJECTIVES:

I. Determine the clinical benefit, in terms of objective response and stable disease rates, in patients treated with this drug.

II. Determine the 1-year median overall survival and progression-free survival in patients treated with this drug.

III. Determine the frequency and severity of toxic effects in patients treated with this drug.

IV. Correlate, preliminarily, pre- and post-treatment plasma vascular endothelial growth factor and soluble vascular cell adhesion molecule with clinical outcomes in patients treated with this drug.

V. Correlate, preliminarily, circulating endothelial cells with clinical outcomes in patients treated with this drug.

VI. Correlate variants of genes in the pathway targeted by this drug and variants of genes involved in the development of hypertension with the antiangiogenic property of this drug in these patients.

OUTLINE:

Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years from study entry.

Inclusion Criteria:

• Histologically confirmed epithelial, sarcomatous, or biphasic malignant pleural mesothelioma

  • Unresectable disease

    • Residual disease after prior cytoreductive surgery allowed

• Measurable disease by CT scan or MRI

• Prior treatment with platinum-based chemotherapy required

• No known CNS metastasis

• Performance status

  • Zubrod 0-2

• WBC >= 3,000/mm^3

• Absolute neutrophil count >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• AST or ALT =< 1.5 times upper limit of normal (ULN)

• Bilirubin normal

• Creatinine =< 1.5 times ULN OR

• Creatinine clearance >= 50 mL/min

• Proteinuria =< 1+ by 2 consecutive dipstick tests taken >= 1 week apart

• No history of familial long QT syndrome

• Mean QTc =< 470 msec

• Systolic BP =< 150 mm Hg AND diastolic BP =< 100 mm Hg

• Must have New York Heart Association class I or II disease

  • Class II must be controlled with treatment

• Able to swallow and/or receive enteral medications via gastrostomy feeding tube

• Not requiring IV alimentation

• No active peptic ulcer

• No intractable nausea or vomiting

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in remission

• No history of hypersensitivity reaction to compounds of similar chemical or biological composition to the study drug

• Prior monoclonal antibody therapy targeting vascular endothelial growth factor (VEGF), VEGF receptor 1(VEGFR1) or VEGF receptor 2 (VEGFR2) allowed

• No other prior immunotherapy or biologic therapy

• No prior thymidine kinase inhibitor against VEGFR1 or VEGFR2

• No concurrent drugs or biologics with proarrhythmic potential

• No more than 1 prior chemotherapy regimen

• At least 28 days since prior chemotherapy (42 days for nitrosoureas or mitomycin) and recovered

• At least 21 days since prior radiotherapy and recovered

• At least 28 days since prior major surgery (e.g., thoracotomy or laparotomy) and recovered

• No prior surgery that would affect absorption

• Stable antihypertensive therapy allowed provided blood pressure (BP) parameters are met

• Concurrent enrollment on SWOG-S9925 allowed

• No concurrent combination antiretroviral therapy for HIV-positive patients