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

NCT00613223 | Completed Phase 1 DMC

• 1 other identifier: Pro00001919
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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 \& 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.

Conditions

Gliosarcoma; Glioblastoma

Keywords

Malignant Gliomas; Etopophos; Toposar; VePesid; Etoposide; Vandetanib; Zactima; ZD6474; VP-16; Brain Tumor; Recurring Malignant Brain Tumor; Gliosarcoma; Glioblastoma; Glioma; Malignant Glioma; GBM

Outcome Measures

Primary Outcomes (1)

• Safety, tolerability, biologic activity, & pharmacokinetic profile of vandetanib when used in combo w etoposide

  6-month progression free survival

Study Arms (1)

Vandetanib and Etoposide

EXPERIMENTAL

Patients will be stratified based on whether they are receiving an enzyme-inducing anti-epileptic drug (EIAED). The dose level of vandetanib will be increased in successive cohorts of subjects. Etoposide will be given daily at a dose of 50 mg/ day for 21 days followed by 7 days with no etoposide.

Drug: Vandetanib and Etoposide

Interventions

Vandetanib and Etoposide DRUG

Vandetanib will be given orally once day. Swallow tablet with 240 ml of non-carbonated water. Initial dose is 100 mg/day for stratum 1 \& 200 mg/day for stratum 2. Etoposide will be taken by mouth in capsule form at a flat dose of 50 mg/day for 1st 21 days of 28-day cycle. You will not take etoposide for following 7 days of the cycle.

Also known as: Vandetanib - Zactima (ZD 6474), Etoposide - VP-16, Etopophos, Toposar, VePesid

Vandetanib and Etoposide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• Annick Desjardins: lead
• AstraZeneca: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at DUKE

MeSH Terms

Conditions

Gliosarcoma; Glioblastoma; Glioma; Brain Neoplasms

Interventions

vandetanib; Etoposide; etoposide phosphate

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Annick Desjardins, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assist Professor of Medicine

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: February 12, 2008
• Study Start: February 1, 2008
• Primary Completion: October 1, 2010
• Study Completion: May 1, 2011
• Last Updated: February 20, 2013

Record last verified: 2013-02

Locations

US (1)