• Response [ Designated as safety issue: No ]
• Overall survival [ Designated as safety issue: No ]
• Toxicity [ Designated as safety issue: Yes ]

• Response
• Overall survival
• Toxicity

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 recurrent glioblastoma multiforme.

OBJECTIVES:

Primary

• Determine the proportion of patients with recurrent glioblastoma multiforme (GM) who are alive and progression free 6 months after starting AZD2171 therapy.

Secondary

• Assess the biological effect of AZD2171 by using the following MRI techniques: dynamic contrast-enhanced imaging; arterial spin-labeling imaging; perfusion-weighted imaging; and diffusion- tensor imaging at serial time points.
• Measure circulating endothelial and progenitor cells and plasma levels of tumstatin, (vascular endothelial growth factor (VEGF)-A and -D, sVEGF receptors, P1GF, platelet-derived growth factor (PDGF)-AA, PDGF-AB, PDGF-BB, Ang1, thrombospondin-1, and interleukin-8 as markers for response to antiangiogenic therapy in recurrent GM.
• Correlate treatment outcomes with pre-AZD2171 tumor specimens with respect to microvascular density, basement membrane and pericyte coverage, and angiopoietin-1 and -2 expression to determine whether these immunohistochemical analyses can be predictive of the response to AZD2171.
• Measure polymorphisms of kdr/flk-1 gene and genetic analysis of HIF1-alpha, TP53, and endothelial nitric oxide synthase genes in the archival tumor specimens.
• Determine the overall survival of patients with recurrent GM treated with AZD2171.
• Determine the radiographic response rate in patients with recurrent GM treated with AZD2171.
• Determine the safety of AZD2171 in this patient population.

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 12 months.

PROJECTED ACCRUAL: A total of 31 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme

• Measurable contrast-enhancing tumor ≥ 1 cm in longest diameter by baseline MRI or CT scan

  • Patient must have been on no steroids OR a stable dose of steroids for ≥ 5 days prior to baseline MRI or CT scan

    • Patients who are on steroids must be maintained on a stable corticosteroid regimen from baseline scan until the start of study treatment
• No intratumoral or peritumoral hemorrhage by MRI

PATIENT CHARACTERISTICS:

• Karnofsky performance status ≥ 60%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other concurrent malignancy within the past 5 years except curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast
• Mini-mental status examination score ≥ 15
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8 g/dL
• Bilirubin normal
• AST/ALT ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171
• Mean QTc ≤ 470 msec (with Bazett's correction) on screening electrocardiogram
• No history of familial long QT syndrome
• No greater than +1 proteinuria on 2 consecutive dipsticks taken ≥ 1 week apart unless first urinalysis shows no protein

• 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/social situations that would limit compliance with study requirements
• No known coagulopathy that increases the risk of bleeding
• No history of clinically significant hemorrhages

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from toxicity of prior therapy
• At least 3 months since prior radiation therapy, including cranial radiation therapy
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• At least 3 weeks since prior molecularly-targeted agents
• At least 4 weeks since prior major surgery
• No more than 2 prior chemotherapy regimens or antineoplastic drugs
• More than 30 days since prior participation in an investigational trial
• At least 2 weeks since prior enzyme-inducing antiepileptic drugs (EIAEDs)

• No concurrent EIAEDs

  • Concurrent non-EIAEDs allowed
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents

• No concurrent vascular endothelial growth factor inhibitors

  • Prior thalidomide or lenolidomide allowed
• No concurrent anticoagulants (e.g., warfarin) or antiplatelet agents including aspirin
• No other concurrent anticancer agents or therapies
• No concurrent grapefruit juice