• Overall response rate (complete response and partial response) [ Designated as safety issue: No ]
  

• Overall survival [ Designated as safety issue: No ]
  
• Progression-free survival [ Designated as safety issue: No ]
  
• Time to treatment failure [ Designated as safety issue: No ]
  
• Relationship between molecular/genetic correlates of the angiogenesis pathway with survival and response [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

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

Secondary

• Determine the clinical benefit, in terms of objective response and stable disease rates, in patients treated with this drug.
• Determine the 1-year median overall survival and progression-free survival in patients treated with this drug.
• Determine the frequency and severity of toxic effects in patients treated with this drug.
• 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.
• Correlate, preliminarily, circulating endothelial cells with clinical outcomes in patients treated with this drug.
• 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: This is a multicenter study.

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.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• AST or ALT ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin normal

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 50 mL/min
• Proteinuria ≤ 1+ by 2 consecutive dipstick tests taken ≥ 1 week apart

Cardiovascular

• 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

Gastrointestinal

• 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

Other

• 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 CONCURRENT THERAPY:

Biologic therapy

• 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 proarrythmic potential

Chemotherapy

• See Disease Characteristics
• No more than 1 prior chemotherapy regimen
• At least 28 days since prior chemotherapy (42 days for nitrosoureas or mitomycin) and recovered

Radiotherapy

• At least 21 days since prior radiotherapy and recovered

Surgery

• See Disease Characteristics
• At least 28 days since prior major surgery (e.g., thoracotomy or laparotomy) and recovered
• No prior surgery that would affect absorption

Other

• 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