Ph I Dose Escalation Trial of Vandetanib in Combo w Etoposide for Malignant Gliomas

Completed · Phase 1

Conditions studied: Gliosarcoma, Glioblastoma

In brief

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 \& not on enzyme-inducing anti-epileptic drugs (EIAEDs) Secondary Objectives: To assess safety \& tolerability of vandetanib + etoposide in this population; To evaluate pharmacokinetics of vandetanib among malignant glioma patients on \& not on EIAEDs when combined with etoposide. Exploratory Objective: To evaluate for evidence of anti-tumor activity of study regimen among recurrent malignant glioma patients including radiographic response rate, 6-month progression free survival (PFS) rate \& median PFS.

Key facts

Study ID

NCT00613223

Run by

Annick Desjardins

People needed

49

Starts

2008-02-01

Expected to finish

2011-05-01

Last updated by the study team

2013-02-20

Who can join

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

You may qualify if…

• 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

You may not qualify if…

• 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

Where it is running

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

Full record on ClinicalTrials.gov

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