Ph I Zactima + Imatinib Mesylate & Hydroxyurea for Pts w Recurrent Malignant Glioma

This is an interventional treatment trial for Glioblastoma focused on measuring GBM, Brain tumor, Zactima, Gleevec, Hydroxyurea, Glioblastoma, Gliosarcoma, Recurrent malignant glioma, ZD6474, Malignant glioma, Imatinib, Droxia, Hydrea, Hydroxycarbamide, Vandetanib Read More

Inclusion Criteria:

• Pts have baseline evaluations performed ≤14days prior to 1st dose of study drug unless otherwise specified. Written informed consent must be obtained from pt prior to enrollment
• Pts w MG who are presenting in 1st, 2nd or 3rd recurrence or relapse
• Pts may not have tumor biopsy <1 wk or surgical resection <2wks
• For stratum of non-EIAED pts, each pt be off all EIAEDs for >2 wks prior to starting study drug; similarly for stratum of EIAED pts, each pt be on EIAED for >2 wks prior to starting study drug
• Pts should be on non-increasing dose of steroids for >7 days prior to obtaining baseline Gd-MRI of brain
• Pts should be on non-increasing dose of steroids for >7 days prior to starting study drug
• Multifocal disease is eligible
• Age >18yrs
• Karnofsky Performance Status (KPS) of >70
• Absolute neutrophil count (ANC) > 1.0 x 10 9/L
• Hgb>g/dL
• Platelets>100 x 10 9/L
• Serum creatinine<1.5 x upper limit of normal (ULN)/measured 24hr creatinine clearance (CrCl) >50 milliliters/min/1.73m
• Life ≥12wks
• Written informed consent obtained prior to any screening procedures

Exclusion Criteria:

• Serum bilirubin >1.5x ULN of reference range
• Serum creatinine >1.5 x Upper Limit of the Reference Range (ULRR)/CrCl <50 milliliters/min
• K<4.0 mmol/L despite supplementation; serum Ca/Mg out of normal range despite supplementation
• alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 x ULRR
• Evidence of severe/uncontrolled systemic disease or any concurrent condition which in Investigator's opinion makes it undesirable for pt to participate in trial or which would jeopardize compliance w protocol
• Clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease >2 within 3 months before entry;/presence of cardiac disease that, in opinion of Investigator, increases risk of ventricular arrhythmia or dysfunction; ejection fraction<50 percent prior to study initiation
• History of arrhythmia-symptomatic/requires treatment/asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded
• Previous history of corrected QT interval (QTc) prolongation as result from other medication that required discontinuation of that medication
• Congenital long QT syndrome/1st degree relative with unexplained sudden death under 40 years
• Presence of left bundle branch block
• QTc with Bazett's correction that is unmeasurable/>480 msec on screening ECG. If pt has QTc >480 msec on screening ECG, screen ECG may be repeated twice. Average QTc from 3 screening ECGs must be <480 msec in order for pt to be eligible for study
• Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes/induce cytochrome P450 3A4 (CYP3A4) function except for EIAEDs
• Hypertension not controlled by medical therapy
• Currently active diarrhea that may affect ability of pt to absorb study regimen/tolerate diarrhea
• Pregnant/breast feeding
• Previous/current malignancies of other histologies <1yr, w exception of cervical carcinoma in situ & adequately treated basal cell/squamous cell carcinoma of skin
• Receipt of any investigational agents within 30 days prior to commencing study treatment unless pt has recovered from all anticipated toxicities of investigational agent
• Last dose of prior chemo discontinued <4 wks before start of study therapy unless pt has recovered from all anticipated toxicities of chemo
• Last radiation therapy (XRT) <4wks before start of study therapy, unless pt has recovered from all anticipated toxicities of XRT
• Any unresolved toxicity > Common Terminology Criteria (CTC) grade 1 from previous anti-cancer therapy
• Previous enrollment/randomization of treatment in present study
• Major surgery <4 wks/incompletely healed surgical incision before starting study therapy
• Pts who have received prior oral VEGFR, EGFR/PDGFR-directed therapies
• Pts who are taking warfarin sodium