Clinical Trial Finder

Criteria:

• - AST/ALT =< 2.5 times upper limit of normal.

• - Creatinine normal OR creatinine clearance >= 60 mL/min.

• - 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.

• - Karnofsky performance status >= 60% - 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.

• - Histologically confirmed glioblastoma multiforme.

• - Platelet count >= 100,000/mm3.

• - Hemoglobin >= 8 g/dL.

• - Bilirubin normal.

• - 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.

• - 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.

• - WBC >= 3,000/mm3.

• - Not pregnant or nursing.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception.

- Absolute neutrophil count >= 1,500/mm3

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

• I. 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.

• II. 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.

• III. 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.

• IV. 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.

• V. Determine the overall survival of patients with recurrent GM treated with AZD2171.

• VI. Determine the radiographic response rate in patients with recurrent GM treated with AZD2171.

• VII. 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.

Arms

Experimental: Arm I

Patients receive oral AZD2171 once daily on days 1-28.

Interventions

Drug: - cediranib maleate

Given orally