Cediranib, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma

Inclusion Criteria:

• Histologically confirmed glioblastoma

  • Newly diagnosed disease
• Scheduled to receive standard post-surgical (i.e., biopsy or resection) temozolomide and radiotherapy
• Must have residual, contrast-enhancing tumor (≥ 1 centimeter in ≥ 1 dimension)
• Patients must be maintained on a stable corticosteroid regimen for 5 days prior to their baseline scan and for 5 days prior to their first vascular MRI; the dose of steroids should remain the same during the baseline vascular MRIs
• Archival tumor tissue available for molecular analysis
• No intratumoral hemorrhage or peritumoral hemorrhage by MRI
• Karnofsky performance status 60-100%
• Leukocytes ≥ 3,000/mcl
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Hemoglobin ≥ 8 g/dL
• Total bilirubin normal
• AST/ALT ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Proteinuria ≤ 1+ on two consecutive dipsticks ≥ 7 days apart
• Mini-mental status examination score ≥ 15

• Must be able to tolerate MRI and must consent to participate in additional Vascular Imaging Procedures per protocol

  • CT scans cannot be substituted for MRI
• Mean QTc ≤ 500 msec (with Bazett's correction) by electrocardiogram

• No concurrent malignancy except curatively treated basal cell or squamous cell carcinoma skin cancer or carcinoma in situ of the cervix or breast

  • Patients with prior malignancies must be disease-free for ≥ 5 years
• No history of familial long QT syndrome or other significant ECG abnormality
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

  • Hypertension (e.g., blood pressure > 140/90 mm Hg)
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations that would preclude study compliance
• No known coagulopathy that increases risk of bleeding
• No history of clinically significant hemorrhages in the past
• No New York Heart Association class III-IV heart disease
• No condition requiring concurrent drugs or biologics with proarrhythmic potential
• No other concurrent chemotherapy agents, investigational agents, or biologic therapy
• No prior chemotherapy, radiotherapy, or any experimental therapy for this disease
• No prior IV bevacizumab for any other medical condition
• No prior carmustine implant (Gliadel Wafer)
• No prior brachytherapy or radiosurgery for this disease
• More than 30 days since prior and no other concurrent investigational agents or participation in an investigational therapeutic trial

• At least 2 weeks since prior and no concurrent enzyme-inducing anti-epileptic drugs (EIAEDs)

  • Concurrent non-EIAEDs allowed
• No concurrent CYP450-inducing anticonvulsants

• No concurrent anticoagulants (e.g., dalteparin, warfarin, or low-molecular weight heparin)

  • If patients require warfarin or other anticoagulants (e.g., low-molecular weight heparin) while on study, then patient may continue treatment
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent VEGF inhibitors
• No concurrent pentamidine
• No concurrent herbal or nontraditional medications