Ph I Gleevec in Combo w RAD001 + Hydroxyurea for Pts w Recurrent MG

Completed · Phase 1

Conditions studied: Glioblastoma, Gliosarcoma

In brief

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 enzyme-inducing anti-convulsants including pts not on anti-epileptic drugs Secondary objective To assess safety \& tolerability of imatinib mesylate in combo w RAD001 \& hydroxyurea in this population To characterize single-dose \& repeated-dose pharmacokinetic profiles of imatinib mesylate \& RAD001 combo therapy in this pt population. To assess antiangiogenic effects, pre- and post-treatment, of imatinib mesylate, RAD001 \& hydroxyurea combo therapy, using DCE-MRI to evaluate changes in extent of vascular permeability, perfusion \& relative tumor blood volume; to explore assessment of tumor cellularity \& tumor cell death by changes in DWI-MRI as quantitated by apparent diffusion coefficient maps.

Key facts

Study ID

NCT00613132

Run by

Annick Desjardins

People needed

78

Starts

2005-05-01

Expected to finish

2013-01-01

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…

• 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

You may not qualify if…

• 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

Where it is running

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

Full record on ClinicalTrials.gov

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