AZD2171 in Treating Patients With Recurrent Glioblastoma Multiforme

Study Overview
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Brief Summary
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This phase II trial is studying how well AZD2171 works in treating patients with recurrent glioblastoma multiforme. 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

Detailed Description
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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.

Official Title
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A Phase II Study of AZD2171 in Recurrent Glioblastoma

Conditions
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Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor

Intervention / Treatment
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* Drug: cediranib maleate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral AZD2171 once daily on days 1-28. | Drug: cediranib maleate<br>* Given orally<br>* Other names: Recentin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients alive and progression-free at 6 months |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic response proportion | Will be described with 95% confidence limits. | Up to 12 months | 
| Overall survival | Will be described with 95% confidence limits. | Up to 12 months | 
| Toxicity proportion | Will be described with 95% confidence limits. | Up to 12 months |