A Phase II Study of AZD2171 in Recurrent Glioblastoma

Inclusion Criteria

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