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

Completed · Phase 1

Conditions studied: Glioblastoma, Gliosarcoma

In brief

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 who are on \& not on enzyme-inducing anti-epileptic drugs Secondary Objectives To assess safety \& tolerability of Zactima + imatinib mesylate \& hydroxyurea To evaluate pharmacokinetics of Zactima among MG pts on \& not on enzyme inducing anti-epileptic drugs (EIAEDs) when combo w imatinib mesylate \& hydroxyurea To evaluate pharmacokinetics of imatinib mesylate among MG pts on \& not on EIAEDs when combo w Zactima \& hydroxyurea Exploratory Objective To evaluate for evidence of anti-tumor activity of study regimen among recurrent malignant glioma (RMG) pts including radiographic response rate, 6-month progression free survival (PFS) rate \& median PFS

Key facts

Study ID

NCT00613054

Run by

Annick Desjardins

People needed

27

Starts

2007-11-01

Expected to finish

2009-04-01

Last updated by the study team

2012-12-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

You may not qualify if…

• 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

Where it is running

• Duke University Health System — Durham, North Carolina, United States

Full record on ClinicalTrials.gov

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