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

NCT00613054 | Completed Phase 1 DMC

• 1 other identifier: Pro00000393
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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 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

Conditions

Glioblastoma; Gliosarcoma

Keywords

GBM; Brain tumor; Zactima; Gleevec; Hydroxyurea; Glioblastoma; Gliosarcoma; Recurrent malignant glioma; ZD6474; Malignant glioma; Imatinib; Droxia; Hydrea; Hydroxycarbamide; Vandetanib

Outcome Measures

Primary Outcomes (1)

• To determine MTD & dose-limiting toxicity (DLT) & Zactima when combo w Imatinib mesylate & Hydroxyurea among pt w Recurrent MG

  6 months

Secondary Outcomes (1)

• To further assess safety & tolerability of Zactima & Imatinib mesylate & Hydroxyurea

  6 months

Study Arms (1)

Zactima + Gleevec + Hydrea

EXPERIMENTAL

Drug: Zactima, Gleevec, Hydroxyurea

Interventions

Zactima, Gleevec, Hydroxyurea DRUG

Pts will start treatment on day 1 of cycle 1 w Zactima, imatinib mesylate \& hydroxyurea. All 3 agents administered in continuous daily, oral manner. Imatinib mesylate dose 400 mg/day for pts not on EIAEDs \& 1000 mg/day for pts on EIAEDs based on previous studies demonstrating that pts on EIAEDs require significantly higher doses of imatinib mesylate \& that such doses are safe \& well tolerated. Dose of hydroxyurea 500 mg twice day. Dose level of Zactima will be increased in successive cohorts of pts as described below. Cohorts of 3-6 pts will accrue at each dose level until MTD is defined. Each cohort will consist of a mini of 3 newly enrolled pts. Intra-patient dose escalation is not permitted. Cohorts may be expanded at any dose level for further elaboration of safety \& pharmacokinetic parameters as required. Treatment cycle is defined as daily administration of Zactima + imatinib mesylate \& hydroxyurea for 28 days for purpose of scheduling evaluations.

Also known as: Zactima-ZD6474-Vandetanib, Gleevec-Imatinib mesylate, Hydroxyurea-Droxia-Hydrea-Hydroxycarbamide

Zactima + Gleevec + Hydrea

Eligibility Criteria

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

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

Sponsors & Collaborators

• Annick Desjardins: lead
• Novartis Pharmaceuticals: collaborator
• 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

Glioblastoma; Gliosarcoma; Brain Neoplasms; Glioma

Interventions

vandetanib; Imatinib Mesylate; Hydroxyurea

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Urea

Study Officials

• Annick Desjardins, MD, FRCPC

  Duke Health

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: February 12, 2008
• Study Start: November 1, 2007
• Primary Completion: March 1, 2009
• Study Completion: April 1, 2009
• Last Updated: December 5, 2012

Record last verified: 2012-12

Locations

US (1)