Zactima With Temodar During Radiation Treatment for Newly Diagnosed Stage IV Brain Tumors

All inclusion and exclusion criteria apply to both phase I and II patients.

Inclusion Criteria

• Subjects with histologically proven intracranial glioblastoma multiforme (GBM) and gliosarcoma will be eligible for this protocol.
• Gadolinium MRI or contrast CT must be obtained within 14 days prior to registration.
• Patients must have a plan to begin treatment with ZD6474 (vandetanib) and/or temozolomide 21 to 35 days after surgical resection or 14 to 35 days after stereotactic biopsy.
• Subjects must have a plan to begin partial brain radiotherapy 5-7 days after beginning ZD6474. Radiotherapy must be a) at the Radiation Oncology Department of the participating institution, b) at an affiliated site that is currently approved to participate in any trial of the Radiation Therapy Oncology Group (RTOG), or c) at another location with prior approval from the Overall PI of the trial. Radiotherapy must be given by external beam to a partial brain field in daily fractions of 180 to 200 cGy, to a planned total dose to the tumor of approximately 6000 cGy. Stereotactic radiosurgery and brachytherapy will not be allowed.
• If it is deemed in the best interest of the patient, intensity modulated radiation therapy (IMRT) is allowable on this trial. If IMRT is administered, dose specifics must be conducted per institutional guidelines.
• Subjects must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while being treated with ZD6474 (ZactimaTM), with the exception of temozolomide.
• All subjects must sign an informed consent indicating that they are aware of the investigational nature of this study prior to any study-related procedures. Patients must be registered with in the Dana Farber Cancer Institute's Quality Assurance Office for Clinical Trials prior to treatment with ZD6474 (Vandetanib). Patients must sign an authorization for the release of their protected health information.
• Subjects can be male or female, and must be >/= 18 years old, with a life expectancy > 12 weeks.
• Subjects must be able to care for themselves (KPS>/=60).
• Subjects must have adequate labs as defined below:
• Patients must have adequate bone marrow function (WBC >/= 3,000/μl, ANC >/= 1,500/mm3, platelet count of >/= 100,000/mm3, and hemoglobin >/= 10 gm/dl), adequate liver function (SGOT, SGPT 30 mL/min, calculated by Cockcroft-Gault formula) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
• Patients must have potassium >/= 4.0 mmol/L and serum calcium (ionized or adjusted for albumin) or magnesium in the normal range (supplementation is allowed).
• Patients' alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be /= 2 within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
• No history of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded.
• No previous history of QTc prolongation as a result from other medication that required discontinuation of that medication.
• No congenital long QT syndrome, or1st degree relative with unexplained sudden death under 40 years of age.
• No left bundle branch block (LBBB).
• Subject's screening ECG cannot indicate QTc (with Bazett's correction) that is either unmeasurable or >/= 480 msec on. If subject's screening QTc >/= 480 msec, it may be repeated twice (at least 24 hours apart). The average QTc from the 3 screening ECGs must be /= 460 msec.
• Subjects must not be taking any enzyme-inducing anti-epileptic drugs (EIAED) or other drugs that are potent inducers of CYP3A4 function (rifampicin, rifabutin,