Status:
COMPLETED
Ph I Gleevec in Combo w RAD001 + Hydroxyurea for Pts w Recurrent MG
Lead Sponsor:
Annick Desjardins
Collaborating Sponsors:
Novartis Pharmaceuticals
Conditions:
Glioblastoma
Gliosarcoma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
Primary objective To determine maximum tolerated dose \& dose limiting toxicity of imatinib mesylate \& RAD001 when combined w fixed doses of hydroxyurea among pts w recurrent GBM who are on \& not on...
Detailed Description
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 p...
Eligibility Criteria
Inclusion
- 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
- 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
Key Trial Info
Start Date :
May 1 2005
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
January 1 2013
Estimated Enrollment :
78 Patients enrolled
Trial Details
Trial ID
NCT00613132
Start Date
May 1 2005
End Date
January 1 2013
Last Update
February 20 2013
Active Locations (1)
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1
Duke University Health System
Durham, North Carolina, United States, 27710