Status:
COMPLETED
Ph I Dose Escalation Trial of Vandetanib in Combo w Etoposide for Malignant Gliomas
Lead Sponsor:
Annick Desjardins
Collaborating Sponsors:
AstraZeneca
Conditions:
Gliosarcoma
Glioblastoma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
Primary Objective: To determine maximum tolerated dose \& dose limiting toxicity of vandetanib when combined with standard dosing of etoposide among patients with recurrent malignant glioma who are on...
Detailed Description
This is open-label, single center, 2-cohort phase I dose-escalation study of vandetanib administered orally on continuous daily dosing schedule + oral etoposide among adult patients with recurrent or ...
Eligibility Criteria
Inclusion
- Patients have baseline evaluations ≤14days prior to 1st dose of study drug unless otherwise specified
- Patients with confirmed malignant glioma (MG) who are recurrence/relapse
- Patients may not have stereotactic tumor biopsy \< 1 week or surgical resection or open biopsy \< 4 weeks before starting study drug
- For stratum of non-EIAED patients, each patient must be off all EIAEDs for \> 2 weeks prior to starting study drug; similarly for stratum of EIAED patients, each patient must be on EIAED for \>2 weeks prior to starting study drug
- Patients should be on non-increasing dose of steroids for \>7 days prior to obtaining baseline MRI with gadolinium (Gd-MRI) of brain
- Patients should be on non-increasing dose of steroids for \>7 days prior to starting study drug
- Multifocal disease is eligible
- Age ≥ 18 years
- Karnofsky Performance Status (KPS) ≥70
- Absolute Neutrophil Count ≥1.0 x 10 9/L
- Hemoglobin (Hgb) ≥9 g/dL
- Platelets ≥100 x 10 9/L
- Serum creatinine ≤1.5 x ULRR or measured 24-hr CrCl ≥50mL/min/1.73m2
- Life expectancy ≥ 12 weeks
- Written informed consent obtained prior to screening procedures
- Negative Beta-HCG pregnancy test for women of child-bearing potential
Exclusion
- Laboratory Results:
- Serum direct bilirubin \>1.5 x upper limit of normal (ULN) of reference range
- Serum creatinine \>1.5 x ULRR \& CrCl \<30 mL/min
- Potassium, \<4.0 mmol/L despite supplementation; serum calcium, magnesium out of normal range despite supplementation
- ALT or AST \> 2.5 x ULRR
- Evidence of severe/uncontrolled systemic disease or any concurrent condition which in Investigator's opinion makes it undesirable for patient to participate in trial or which would jeopardize compliance with protocol
- Clinically significant cardiovascular event such as myocardial infarction, superior vena cava syndrome, New York Heart Association classification of heart disease \>2 within 3 months before entry; or presence of cardiac disease that, in opinion of Investigator, increases risk of ventricular arrhythmia
- History of arrhythmia which is symptomatic/requires treatment/asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded.
- Previous history of QTc prolongation as result from other medication that required discontinuation of that medication
- Congenital long QT syndrome, or 1st degree relative with unexplained sudden death \<40 years
- Presence of left bundle branch block
- QTc with Bazett's correction that's unmeasureable, or ≥ 480msec on screening EEG.
- Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes/induce CYP3A4 function except for EIAEDs
- Hypertension not controlled by medical therapy
- Currently active diarrhea that may affect ability of patient to absorb study regimen/tolerate diarrhea
- Women who are currently pregnant/breast feeding
- Previous or current malignancies of other histologies the last year, with exception of cervical carcinoma in situ \& adequately treated basal cell or squamous cell carcinoma of skin
- Receipt of any investigational agents \<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 weeks before start of study therapy unless pt has recovered from all anticipated toxicities of chemo
- Last XRT \< 4 weeks before start of study therapy, unless patient has recovered from all anticipated toxicities of XRT
- Any unresolved toxicity \>CTC gr1 from previous anti-cancer therapy
- Previous enrollment/randomization of treatment in present study
- Major surgery \< 4 weeks/incompletely healed surgical incision before starting study therapy
- Patients who have received prior oral VEGFR, EGFR or PDGFR-directed therapies. Patients who received prior Avastin will be eligible as long as at least 6 weeks has elapsed since last dose.
- Patients taking warfarin sodium
Key Trial Info
Start Date :
February 1 2008
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 1 2011
Estimated Enrollment :
49 Patients enrolled
Trial Details
Trial ID
NCT00613223
Start Date
February 1 2008
End Date
May 1 2011
Last Update
February 20 2013
Active Locations (1)
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1
Duke University Health System
Durham, North Carolina, United States, 27710