GlioblastomaPhase 2NCT00615927
Phase II Imatinib + Hydroxyurea in Treatment of Patients With Recurrent/Progressive Grade II Low-Grade Glioma (LGG)
A Phase 2 study testing Imatinib Mesylate & Hydroxyurea in people with Glioblastoma and Gliosarcoma, run by Duke University at 1 site in United States.
Trial summary
Primary objective: To evaluate activity of imatinib mesylate and hydroxyurea among patients with progressive/recurrent grade II low-grade glioma (LGG) as measured by 12-month progression free survival Secondary objectives: To evaluate progression-free survival (PFS), overall survival and objective response rate among… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Glioblastoma, Gliosarcoma
- What is being tested?
- Imatinib Mesylate & Hydroxyurea
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2006to Jun 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients with grade II LGG that is recurrent/progressive following prior surgical resection while on non-decreasing dose of corticosteroids
- > 25percent enlargement of bidimensional measure/new lesions on sequential imaging new \&/or worsening neurologic deficits
- Patients with progressive/recurrent optic pathway tumors
- Patients have measurable disease on MRI/CT
- Interval of > 4 wks between prior external beam radiation therapy (XRT)/chemo,\& enrollment on protocol unless there is unequivocal evidence of tumor progression \& patient has recovered from all expected toxicities associated with prior therapy. Patients treated w chemo agents such as VP-16 who would normally be retreated after shorter intervals may be treated at usual starting time even if < 4 wks from last prior dose of chemo
- Patients not have had tumor biopsy < 1 wk/surgical resection < 2 wks prior to starting study drug
Show all 23Show fewer
- Patients enrolling on arm B must be on > 1 enzyme inducing anticonvulsants for >2 wks prior to starting study drug
- Patients should be on non-increasing dose of steroids for > 7 days prior to obtaining baseline Gd-MRI of brain
- Patients should be on non-increasing dose of steroids for > 7 days prior to starting study drug
- Multifocal disease is eligible
- Age > 18 yrs old
- Karnofsky Performance Status (KPS) of > 60
- absolute neutrophil count (ANC) > 1.5 x 10 9/L
- Hgb > 9 g/dL
- Platelets > 100 x 10 9/L
- K ≥ lower limit of normal (LLN)/correctable with supplements
- Ca ≥ LLN/correctable with supplements
- P ≥ LLN/correctable with supplements
- aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) \& Alanine transaminase (ALT)/ Serum Glutamic Pyruvate Transaminase (SGPT} < 2.5 x ULN
- Serum bilirubin < 1.5 x upper limit of normal (ULN)
- Serum creatinine < 1.5 x ULN/measured 24hr Creatinine Clearance > 50 mL/min/1.73m2
- Life expectancy ≥ 12wks
- Written informed consent obtained prior to screening procedures
Who cannot join
- Prior progressive disease/toxicity grade ≥ 3 with prior hydroxyurea therapy
- Prior treatment with imatinib/other platelet derived growth factor (PDGF)-directed therapy
- Excessive risk of bleeding as defined by stroke < 6 months, history of central nervous system (CNS)/intraocular bleed, or septic endocarditis
- Evidence of intratumor hemorrhage on pretreatment diagnostic imaging, except for stable post-operative gr1 hemorrhage
- Pregnant/breast feeding, /adults of reproductive potential not employing effective method of birth control
- Concurrent severe and/or uncontrolled medical disease that could compromise participation in study
Show all 23Show fewer
- Acute/chronic liver disease
- Confirmed diagnosis of HIV infection
- Impairment of GI function/GI disease that may significantly alter absorption of imatinib
- Patients taking Coumadin
- Patients have received investigational drugs < 2wks prior to entry on study/have not recovered from toxic effects of such therapy
- Patients have received biologic, immunotherapeutic/cytostatic agents < 1 wk prior to entry on study/have not recovered from toxic effects of such therapy
- Patient > 5 yrs free of another primary malignancy except: if other primary malignancy is not currently clinically significant/requiring active intervention, or if other primary malignancy is basal cell skin cancer/ cervical carcinoma in situ. Existence of any other malignant disease is not allowed
- Patients have had any surgery other than resection of brain tumor < 2 wks prior to entry on study/have not recovered from side effects of such therapy
- Patients unwilling to/unable to comply with protocol
- Active systemic bleeding, such as GI bleeding/gross hematuria
- Gr2 /> peripheral edema/central/systemic fluid collections
- Patients who enroll on arm A must have not received any EIAC for > 2 wks prior to starting study regimen
- Any of following exclusion criteria to MRI imaging:
- Cardiac pacemaker
- Ferromagnetic metal implants other than those approved as safe for use in magnetic resonance (MR) scanners
- Claustrophobia
- Obesity
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 II Study of Imatinib Mesylate Plus Hydroxyurea in the Treatment of Patients With Recurrent / Progressive Grade II Low-Grade Glioma
Primary objective:
- To evaluate activity of imatinib mesylate and hydroxyurea among patients with progressive/recurrent grade II low-grade glioma (LGG) as measured by 12-month progression free survival
Secondary objectives:
- To evaluate progression-free survival (PFS), overall survival and objective response rate among patients with progressive/recurrent grade II LGG treated with imatinib mesylate plus hydroxyurea
- To assess safety and tolerability of imatinib mesylate + hydroxyurea in this population
Read the detailed description
This is an open-label, single stage, uncontrolled, non-randomized Phase II study of continuous, daily doses of imatinib mesylate \& hydroxyurea in adult patients with progressive/recurrent Grade II low-grade glioma (LGG). The treatment cycle is defined as imatinib mesylate \& hydroxyurea administered daily for 28 days for purpose of scheduling evaluations. All patients who receive 1 or more doses of either imatinib mesylate or hydroxyurea will be evaluable for toxicity, whereas all patients who receive a minimum of 14 consecutive days of study regimen will be evaluable for response. Patients who discontinue therapy prior to receiving 14 consecutive days of study regimen will be regarded as ineligible for evaluation of response and will be replaced.
- Conditions
- Glioblastoma, Gliosarcoma
- Being tested
- Imatinib Mesylate & Hydroxyurea
- Keywords
- Glioblastoma, Gliosarcoma, glioblastoma multiforme (GBM), GBM, Imatinib Mesylate, Gleevec, Hydroxyurea, Droxia, Hydrea, Hydroxycarbamide, Imatinib, Brain tumor, Malignant brain tumor, Recurrent glioblastoma multiforme, Progressive 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.
Imatinib Mesylate & HydroxyureaDrug
Also called Imatinib Mesylate-Gleevec, Hydroxyurea-Droxia-Hydrea-Hydroxycarbamide
Imatinib administered orally on daily. Imatinib is local irritant \& must be taken in sitting position; mini of 2hrs should be allowed between last drug intake \& going to bed. Imatinib doses 400mg/600mg administered once daily, whereas daily doses of 800mg/> administered as equally divided dose taken twice day. Dose for imatinib: Pts not receiving p450-inducing antiepileptic drugs: 400 mg/day. Pts receiving p450-inducing antiepileptic drugs: 500 mg twice day. It is recommended that pts take their prescribed imatinib mesylate at same time that they take their prescribed hydroxyurea, however, 30-60min interval between agents is acceptable if required for practical/other compliance issues.
Hydroxyurea administered orally twice day. Dosing will begin on day 1 of cycle 1 \& continue daily. Drug is approximately 80 percent bioavailable. Dose will be 500mg twice day for all pts.
| Study group | Role | What they receive |
|---|---|---|
| Astrocytoma | Experimental | Grade II Astrocytoma Receives: Drug: Imatinib Mesylate & Hydroxyurea |
| Oligodendroglioma | Experimental | Grade II Oligodendroglioma or oligoastrocytomas Receives: Drug: Imatinib Mesylate & Hydroxyurea |
What is being measured
The primary outcome is the main question the study is designed to answer.
12-month Progression Free Survival (PFS)
Percentage of participants surviving twelve months from the start of cycle 1 without progression of disease. PFS was defined as the time from the cycle 1 start date to the date of the first documented progression according to modified Macdonald criteria, or to death due to any cause.
Measured: 12 months
Secondary outcomes (4)
Median Progression-free Survival
Time in weeks from the start of cycle 1 to the date of first progression according to modified Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.
Measured: Time in weeks from the start of cycle 1 to the date of first progression according to modified Macdonald criteria or to death due to any cause, assessed up to 156 weeks
Median Overall Survival (OS)
Time in weeks from the start of cycle 1 to date of death due to any cause. Patients alive at last follow-up are censored as of that follow-up date. Median OS was estimated using a Kaplan-Meier curve.
Measured: Time in weeks from the start of cycle 1 to date of death due to any cause, assessed up to 156 weeks
Objective Response Rate
Number of participants with an objective response (complete response or partial response) based on modified Macdonald criteria.
Measured: 156 weeks
Safety and Tolerability of Gleevec + Hydroxyurea in Patients With Low-grade Gliomas
The number of patients experiencing any serious adverse event or other (non-serious) adverse event during the study participation.
Measured: 156 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2008 (estimated)
- Study startFeb 2006
- Primary completionApr 2009
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Annick Desjardins, MD, FRCPC, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00615927
- Sponsor's protocol ID
- Pro00008799
- Status last verified
- Dec 2012
- First submitted
- 3 Feb 2008
- Last updated
- 15 Mar 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Imatinib Mesylate Plus Hydroxyurea in the Treatment of Patients With Recurrent / Progressive Grade II Low-Grade Glioma
- ClinicalTrials.gov ID
- NCT00615927
- Acronym / sponsor ID
- Pro00008799
- Conditions
- Glioblastoma, Gliosarcoma
- Keywords
- Glioblastoma, Gliosarcoma, glioblastoma multiforme (GBM), GBM, Imatinib Mesylate, Gleevec, Hydroxyurea, Droxia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Feb 2006
- Primary completion
- Apr 2009 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 14 Feb 2008 (estimated)
- Results
- Posted 15 Mar 2013
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 evaluate activity of imatinib mesylate and hydroxyurea among patients with progressive/recurrent grade II low-grade glioma (LGG) as measured by 12-month progression free survival
Secondary objectives:
- To evaluate progression-free survival (PFS), overall survival and objective response rate among patients with progressive/recurrent grade II LGG treated with imatinib mesylate plus hydroxyurea
- To assess safety and tolerability of imatinib mesylate + hydroxyurea in this population
Detailed description
This is an open-label, single stage, uncontrolled, non-randomized Phase II study of continuous, daily doses of imatinib mesylate \& hydroxyurea in adult patients with progressive/recurrent Grade II low-grade glioma (LGG). The treatment cycle is defined as imatinib mesylate \& hydroxyurea administered daily for 28 days for purpose of scheduling evaluations. All patients who receive 1 or more doses of either imatinib mesylate or hydroxyurea will be evaluable for toxicity, whereas all patients who receive a minimum of 14 consecutive days of study regimen will be evaluable for response. Patients who discontinue therapy prior to receiving 14 consecutive days of study regimen will be regarded as ineligible for evaluation of response and will be replaced.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Astrocytoma | Experimental | Drug: Imatinib Mesylate & HydroxyureaGrade II Astrocytoma |
| Oligodendroglioma | Experimental | Drug: Imatinib Mesylate & HydroxyureaGrade II Oligodendroglioma or oligoastrocytomas |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Patients with grade II LGG that is recurrent/progressive following prior surgical resection while on non-decreasing dose of corticosteroids
- > 25percent enlargement of bidimensional measure/new lesions on sequential imaging new \&/or worsening neurologic deficits
- Patients with progressive/recurrent optic pathway tumors
- Patients have measurable disease on MRI/CT
- Interval of > 4 wks between prior external beam radiation therapy (XRT)/chemo,\& enrollment on protocol unless there is unequivocal evidence of tumor progression \& patient has recovered from all expected toxicities associated with prior therapy. Patients treated w chemo agents such as VP-16 who would normally be retreated after shorter intervals may be treated at usual starting time even if < 4 wks from last prior dose of chemo
Key exclusion criteria (23 listed)
- Prior progressive disease/toxicity grade ≥ 3 with prior hydroxyurea therapy
- Prior treatment with imatinib/other platelet derived growth factor (PDGF)-directed therapy
- Excessive risk of bleeding as defined by stroke < 6 months, history of central nervous system (CNS)/intraocular bleed, or septic endocarditis
- Evidence of intratumor hemorrhage on pretreatment diagnostic imaging, except for stable post-operative gr1 hemorrhage
- Pregnant/breast feeding, /adults of reproductive potential not employing effective method of birth control
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 |
|---|---|---|
| Imatinib Mesylate & HydroxyureaAlso: Imatinib Mesylate-Gleevec, Hydroxyurea-Droxia-Hydrea-HydroxycarbamideImatinib administered orally on daily. Imatinib is local irritant \& must be taken in sitting position; mini of 2hrs should be allowed between last drug intake \& going to bed. Imatinib doses 400mg/600mg administered once daily, whereas daily doses of 800mg/> administered as equally divided dose taken twice day. Dose for imatinib: Pts not receiving p450-inducing antiepileptic drugs: 400 mg/day. Pts receiving p450-inducing antiepileptic drugs: 500 mg twice day. It is recommended that pts take their prescribed imatinib mesylate at same time that they take their prescribed hydroxyurea, however, 30-60min interval between agents is acceptable if required for practical/other compliance issues. Hydroxyurea administered orally twice day. Dosing will begin on day 1 of cycle 1 \& continue daily. Drug is approximately 80 percent bioavailable. Dose will be 500mg twice day for all pts. | Drug | Astrocytoma, Oligodendroglioma |
Primary outcome
12-month Progression Free Survival (PFS)
Time frame: 12 months
Percentage of participants surviving twelve months from the start of cycle 1 without progression of disease. PFS was defined as the time from the cycle 1 start date to the date of the first documented progression according to modified Macdonald criteria, or to death due to any cause.
4 secondary outcomes
Median Progression-free Survival
Time frame: Time in weeks from the start of cycle 1 to the date of first progression according to modified Macdonald criteria or to death due to any cause, assessed up to 156 weeks
Median Overall Survival (OS)
Time frame: Time in weeks from the start of cycle 1 to date of death due to any cause, assessed up to 156 weeks
Objective Response Rate
Time frame: 156 weeks
Safety and Tolerability of Gleevec + Hydroxyurea in Patients With Low-grade Gliomas
Time frame: 156 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The Preston Robert Tisch Brain Tumor Center at DUKELink provided by the sponsor.
Related trials for Glioblastoma
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
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, FRCPC 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 2 study testing Imatinib Mesylate & Hydroxyurea in people with Glioblastoma and Gliosarcoma, run by Duke University 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 23 inclusion and 23 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 15 Mar 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
12-month Progression Free Survival (PFS) (time frame: 12 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 15 Mar 2013.