Status:
COMPLETED
Ph I Zactima + Imatinib Mesylate & Hydroxyurea for Pts w Recurrent Malignant Glioma
Lead Sponsor:
Annick Desjardins
Collaborating Sponsors:
Novartis Pharmaceuticals
AstraZeneca
Conditions:
Glioblastoma
Gliosarcoma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
Primary Objective To determine maximum tolerated dose \& dose limiting toxicity of Zactima when combined w standard dosing of imatinib mesylate \& hydroxyurea among pts w recurrent malignant glioma wh...
Detailed Description
vascular endothelial growth factor (VEGF) angiogenic \& Phosphoinositide 3-kinase inhibitor/Protein Kinase B (PI3K/AKT) mitogenic cascades are 2 upregulated cell signalling pathways in MG that contrib...
Eligibility Criteria
Inclusion
- 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
- 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
Key Trial Info
Start Date :
November 1 2007
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 1 2009
Estimated Enrollment :
27 Patients enrolled
Trial Details
Trial ID
NCT00613054
Start Date
November 1 2007
End Date
April 1 2009
Last Update
December 5 2012
Active Locations (1)
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1
Duke University Health System
Durham, North Carolina, United States, 27710