NCT00613132

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 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
78

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started May 2005

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2005

Completed
2.7 years until next milestone

First Submitted

Initial submission to the registry

January 29, 2008

Completed
14 days until next milestone

First Posted

Study publicly available on registry

February 12, 2008

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2008

Completed
4.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2013

Completed
Last Updated

February 20, 2013

Status Verified

February 1, 2013

Enrollment Period

3.3 years

First QC Date

January 29, 2008

Last Update Submit

February 19, 2013

Conditions

GlioblastomaGliosarcoma

Keywords

GlioblastomaGliosarcomaGBMBrain tumorRAD0001HydroxyureaGleevecImatinibDroxiaEverolimusHydreaHydroxycarbamideRecurrent GBMImatinib mesylateGlioblastoma multiforme

Outcome Measures

Primary Outcomes (1)

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

    6 months

Secondary Outcomes (2)

  • To further evaluate safety & tolerability & Imatinib mesylate in combo w RAD001 & Hydroxyurea

    6 months

  • To evaluate PK on Imatinib mesylate when administered w RAD001 among GBM pt who are on & not on EIAEDs

    6 months

Study Arms (2)

1

EXPERIMENTAL

Pts receiving EIACDs

Drug: Gleevec, RAD001, and Hydroxyurea

2

EXPERIMENTAL

Pts not receiving EIACDs

Drug: Gleevec, RAD001, and Hydroxyurea

Interventions

Gleevec, RAD001, and HydroxyureaDRUG

Dose of Gleevec will be 400 mg in 1st cohort \& will be increased to 600 mg po/day \& then to 400 mg bid in successive cohorts. Prescribed dose should be administered orally, w large glass of water. Pts should not eat large or high fat meal within 1 hour before or after gleevec dosing. Doses of 600 mg or less should be administered once daily, whereas doses greater than 600 mg should be administered as equal doses twice day. It is recommended that pts take their prescribed Gleevec at same time that they take their prescribed RAD001 \& hydroxyurea, however, 30-60 minute interval between agents is acceptable if required for practical or other compliance issues.

Also known as: Gleevec-Imatinib-Imatinib mesylate, RAD001-Everolimus, Hydroxyurea-Droxia-Hydrea-Hydroxycarbamide
12

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

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
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Links

MeSH Terms

Conditions

GlioblastomaGliosarcomaBrain Neoplasms

Interventions

Imatinib MesylateEverolimusHydroxyurea

Condition Hierarchy (Ancestors)

AstrocytomaGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueCentral Nervous System NeoplasmsNervous System NeoplasmsNeoplasms by SiteBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

BenzamidesAmidesOrganic ChemicalsBenzoatesAcids, CarbocyclicCarboxylic AcidsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPiperazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPyrimidinesSirolimusMacrolidesLactonesUrea

Study Officials

  • Annick Desjardins, MD

    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

May 1, 2005

Primary Completion

August 1, 2008

Study Completion

January 1, 2013

Last Updated

February 20, 2013

Record last verified: 2013-02

Locations

US(1)