AZD2171 in Treating Patients With Recurrent Glioblastoma Multiforme

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