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Phase I Dose Escalation of Gleevec in Combination With RAD001 Plus Hydroxyurea for Patients With Recurrent Malignant Glioma


Phase 1
18 Years
N/A
Not Enrolling
Both
Glioblastoma, Gliosarcoma

Thank you

Trial Information

Phase I Dose Escalation of Gleevec in Combination With RAD001 Plus Hydroxyurea for Patients With Recurrent Malignant Glioma


This is open-label, single center, 1-arm ph I dose-escalation study of continuous, daily
doses of imatinib mesylate & RAD001 administered orally in combination w fixed doses of
hydroxyurea in adult pts w recurrent or relapsing glioblastoma multiforme. Study format
includes classical "3+3" dose escalation design to determine MTD & DLT of imatinib mesylate
+ RAD001 when combined w hydroxyurea among GBM pts. Pts will be stratified based on whether
they who are receiving EIACD & each stratum will independently dose escalate. Additionally,
study will characterize safety, tolerability, biologic activity, & pharmacokinetic profile
of this combo therapy.


Inclusion Criteria:



- Pts w confirmed GBM, GS, AA, AO & AOA are presenting in 1st, 2nd/3rd
recurrence/relapse

- Pts without tumor biopsy <1 wk/surgical resection <2 wks prior to starting study drug

- For stratum of non-EIAED pts, each pts off all enzyme inducing anticonvulsants 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

- Pts w previous implantation of Gliadel may be eligible after discussion between
investigator & sponsor

- Multifocal disease is eligible

- Age >18 yrs

- KPS >70

- Hematology: ANC>1.5 x 10^9/L, Hgb>9 g/dL, Platelets>100 x 10^9/L

- Biochemistry: K≥ LLN/correctable w supplement, Total Ca≥ LLN/correctable w
supplement, Mg≥ LLN/correctable w supplement, P≥ LLN/correctable w supplement,
AST/SGOT & ALT/SGPT <2.5 x ULN, Serum bilirubin <1.5 x ULN, Serum creatinine <1.5 x
ULN/measured 24hr CrCl<0 mL/min/1.73m2, & Cholesterol≤ 00 mg/dL & triglyceride≤2.5
ULN

- Life expectancy ≥12wks

- Written informed consent obtained prior to any screening procedures

Exclusion Criteria:

- Pts w any peripheral neuropathy ≥CTCAE gr2

- Pts w unresolved diarrhea ≥CTCAE gr2

- History of impaired cardiac function

- Obligate use of cardiac pacemaker, Congenital long QT syndrome, History or presence
of ventricular or atrial tachyarrhythmias, Clinically significant resting bradycardia
, Right bundle branch block + left anterior hemiblock

- Other clinically significant cardiac diseases

- Uncontrolled Db

- Active or uncontrolled infection requiring intravenous antibiotics

- Impairment of GI function/GI disease that may significantly alter absorption of
Gleevec, hydroxyurea and/or RAD001

- Acute/chronic liver/renal disease

- Other concurrent severe and/or uncontrolled medical condition that could cause
unacceptable safety risks/compromise compliance w protocol

- Treatment w any hematopoietic colony-stimulating factor ≤2wks prior to starting study
drug. Erythropoietin is allowed

- Pts w history of CHF/arrhythmias who are receiving treatment w digoxin/verapamil, &
treatment cannot be discontinued/switched to different drug prior to starting study
drug

- Pts taking warfarin sodium

- Pts received treatment w PDGF/mTOR directed therapies

- Pts received chemo ≤ 4wks prior to starting study drug/have not recovered from side
effects of such therapy

- Pts received immunotherapy ≤2 wks prior to starting study drug/have not recovered
from side effects of such therapy

- Pts received investigational drugs ≤4 wks prior to starting study drug/have not
recovered from side effects of such therapy

- Pts received XRT ≤4 wks prior to starting study drug/have not recovered from side
effects of such therapy

- Pts undergone major non-CNS surgery ≤2 wks prior to starting study drug/pts have not
recovered from side effects of such therapy

- Cardiac pacemaker, Ferromagnetic metal implants other than those approved as safe for
use in MR scanners, Claustrophobia, Obesity

- Female pts are pregnant/breast feeding,/adults of reproductive potential not
employing effective method of birth control. Barrier contraceptives must be used
throughout trial in both sexes. Oral, implantable/injectable contraceptives may be
affected by cytochrome P450 interactions, & are therefore not considered effective
for study. Women of childbearing potential have negative serum pregnancy test 48hrs
prior to administration of Gleevec, hydroxyurea and/or RAD001.

- Known diagnosis of HIV infection

- Pts w history of another primary malignancy that is currently clinically
significant/currently requires active intervention

- Pts unwilling to/unable to comply w protocol

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine MTD & DLT & Imatinib mesylate & RAD001 when combined w Hydroxyurea among pt w GBM

Outcome Time Frame:

6 months

Safety Issue:

No

Principal Investigator

Annick Desjardins, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University Health System

Authority:

United States: Food and Drug Administration

Study ID:

Pro00005875

NCT ID:

NCT00613132

Start Date:

May 2005

Completion Date:

January 2013

Related Keywords:

  • Glioblastoma
  • Gliosarcoma
  • Glioblastoma
  • Gliosarcoma
  • GBM
  • Brain tumor
  • RAD0001
  • Hydroxyurea
  • Gleevec
  • Imatinib
  • Droxia
  • Everolimus
  • Hydrea
  • Hydroxycarbamide
  • Recurrent GBM
  • Imatinib mesylate
  • Glioblastoma multiforme
  • Glioblastoma
  • Gliosarcoma

Name

Location

Duke University Health SystemDurham, North Carolina  27705