GlioblastomaPhase 1NCT00613132
Ph I Gleevec in Combo w RAD001 + Hydroxyurea for Pts w Recurrent MG
A Phase 1 study testing Gleevec, RAD001, and Hydroxyurea in people with Glioblastoma and Gliosarcoma, run by Annick Desjardins at 1 site in United States.
Trial 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 \&… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Gliosarcoma
- What is being tested?
- Gleevec, RAD001, and Hydroxyurea
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- May 2005to Jan 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Health System
Durham, North Carolina, 27710
About this study
Official title: Phase I Dose Escalation of Gleevec in Combination With RAD001 Plus Hydroxyurea for Patients With Recurrent Malignant Glioma
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.
Read the 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 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.
- Conditions
- Glioblastoma, Gliosarcoma
- Being tested
- Gleevec, RAD001, and Hydroxyurea
- Keywords
- Glioblastoma, Gliosarcoma, GBM, Brain tumor, RAD0001, Hydroxyurea, Gleevec, Imatinib, Droxia, Everolimus, Hydrea, Hydroxycarbamide, Recurrent GBM, Imatinib mesylate, Glioblastoma multiforme
- Medical subject headings
- Glioblastoma, Gliosarcoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gleevec, RAD001, and HydroxyureaDrug
Also called Gleevec-Imatinib-Imatinib mesylate, RAD001-Everolimus, Hydroxyurea-Droxia-Hydrea-Hydroxycarbamide
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Pts receiving EIACDs Receives: Drug: Gleevec, RAD001, and Hydroxyurea |
| 2 | Experimental | Pts not receiving EIACDs Receives: Drug: Gleevec, RAD001, and Hydroxyurea |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine MTD & DLT & Imatinib mesylate & RAD001 when combined w Hydroxyurea among pt w GBM
Measured: 6 months
Secondary outcomes (2)
To further evaluate safety & tolerability & Imatinib mesylate in combo w RAD001 & Hydroxyurea
Measured: 6 months
To evaluate PK on Imatinib mesylate when administered w RAD001 among GBM pt who are on & not on EIAEDs
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2008 (estimated)
- Study startMay 2005
- Primary completionAug 2008
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Annick Desjardins
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor-investigator, Annick Desjardins, Duke University
- Investigators
- Annick Desjardins, MD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00613132
- Sponsor's protocol ID
- Pro00005875
- Other IDs
- 7020-07-32
- Status last verified
- Feb 2013
- First submitted
- 29 Jan 2008
- Last updated
- 20 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Escalation of Gleevec in Combination With RAD001 Plus Hydroxyurea for Patients With Recurrent Malignant Glioma
- ClinicalTrials.gov ID
- NCT00613132
- Acronym / sponsor ID
- Pro00005875
- Conditions
- Glioblastoma, Gliosarcoma
- Keywords
- Glioblastoma, Gliosarcoma, GBM, Brain tumor, RAD0001, Hydroxyurea, Gleevec, Imatinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Annick DesjardinsUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- May 2005
- Primary completion
- Aug 2008 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 12 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Gleevec, RAD001, and HydroxyureaPts receiving EIACDs |
| 2 | Experimental | Drug: Gleevec, RAD001, and HydroxyureaPts not receiving EIACDs |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gleevec, RAD001, and HydroxyureaAlso: Gleevec-Imatinib-Imatinib mesylate, RAD001-Everolimus, Hydroxyurea-Droxia-Hydrea-HydroxycarbamideDose 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. | Drug | 1, 2 |
Primary outcome
To determine MTD & DLT & Imatinib mesylate & RAD001 when combined w Hydroxyurea among pt w GBM
Time frame: 6 months
2 secondary outcomes
To further evaluate safety & tolerability & Imatinib mesylate in combo w RAD001 & Hydroxyurea
Time frame: 6 months
To evaluate PK on Imatinib mesylate when administered w RAD001 among GBM pt who are on & not on EIAEDs
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2013.
- The Preston Robert Tisch Brain Tumor Center at DUKELink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annick Desjardins, MD principal investigator
Duke Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gleevec, RAD001, and Hydroxyurea in people with Glioblastoma and Gliosarcoma, run by Annick Desjardins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine MTD & DLT & Imatinib mesylate & RAD001 when combined w Hydroxyurea among pt w GBM (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2013.