• Changes in laboratory correlates [ Designated as safety issue: No ]
• Pharmacogenomics by correlating genetic polymorphisms with drug activity and toxicity [ Designated as safety issue: Yes ]

RATIONALE: 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.

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

OBJECTIVES:

Primary

• Determine the objective response rate in patients with malignant pleural, peritoneal, or tunica vaginalis mesothelioma that is not amenable to curative surgery who are treated with AZD2171.

Secondary

• Determine the progression-free survival of patients treated with AZD2171.
• Determine the toxicity experienced by patients treated with AZD2171.
• Determine median and overall survival of patients treated with AZD2171.

Tertiary

• Generate preliminary data regarding potential utility of pharmacogenomic and plasma/serum biomarkers of angiogenesis as predictive or prognostic markers for future investigations of this drug in malignant mesothelioma.

OUTLINE: This is a multicenter study.

Patients receive oral ADZ2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection periodically during study for biomarker and optional pharmacogenomic correlative studies.

After completion of study treatment, patients are followed for up to 8 weeks.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

• Drug: cediranib maleate
• Other: laboratory biomarker analysis

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignant pleural, peritoneal, or tunica vaginalis mesothelioma

  • Epithelial, sarcomatoid, or mixed subtype
• International Mesothelioma Interest Group stage II-IV disease (for patients with pleural mesothelioma)

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR > 10 mm by spiral CT scan

  • Pleural effusion and ascites are not considered measurable lesions
• Disease not amenable to curative surgery
• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
• Life expectancy > 3 months
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Hemoglobin ≥ 8 g/dL
• Platelets ≥ 100,000/mm³
• Total bilirubin normal
• AST/ALT ≤ 2.5 times upper limit of normal (ULN)
• Creatinine normal OR creatinine clearance > 60 mL/min
• Fertile patients must use effective contraception
• Not pregnant or nursing
• Negative pregnancy test
• No history of allergic reactions to compounds of similar chemical or biologic composition to AZD2171
• Mean QTc ≤ 500 msec (with Bazett's correction) by EKG
• No history of long QT syndrome
• Proteinuria ≤ 1+ on two consecutive dipsticks taken ≥ 1 week apart
• No other concurrent malignancy
• No New York Heart Association class III or IV cardiac disease

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

  • Hypertension
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situations that would limit study compliance

PRIOR CONCURRENT THERAPY:

• No more than 1 prior cytotoxic chemotherapy

  • Prior intrapleural cytotoxic agents (including bleomycin) do not count towards prior cytotoxic chemotherapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• No prior radiotherapy to the only site of measurable disease
• At least 4 weeks since prior radiotherapy and recovered
• At least 4 weeks since prior major surgery and recovered
• More than 30 days since prior participation in an investigational trial
• No prior treatment with a vascular endothelial growth factor (VEGF) inhibitor
• No other concurrent investigational agents
• No concurrent commercial agents for the malignancy
• No concurrent medication that may markedly affect renal function (e.g., vancomycin, amphotericin, or pentamidine)
• No concurrent hematopoietic growth factors except epoetin alfa
• No concurrent palliative radiotherapy
• No combination antiretroviral therapy for HIV-positive patients
• No concurrent drugs or biologics with proarrhythmic potential