Recurrent Glioblastoma Multiforme (GBM)Phase 2NCT00290771
Efficacy and Safety of Imatinib Mesylate Plus Hydroxyurea (HU) in Patients With Recurrent Glioblastoma Multiforme (GBM)
A Phase 2 study testing Imatinib tablets and Hydroxyurea capsules in people with Recurrent Glioblastoma Multiforme (GBM), run by Novartis at 1 site in United States.
Trial summary
This was an investigational study to assess the objective overall response (OOR) rate (complete response [CR] + partial response [PR]) of imatinib mesylate and hydroxyurea (hydroxycarbamide) combination therapy in patients with recurrent glioblastoma multiforme (brain tumors). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Glioblastoma Multiforme (GBM)
- What is being tested?
- Imatinib tablets and Hydroxyurea capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 231 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2006to Aug 2008
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females ≥ 18 years old.
- Histologically-confirmed diagnosis of progressive primary glioblastoma multiforme (GBM) based on original diagnosis. Patients with prior low-grade glioma were eligible if histological re-assessment demonstrated transformation to GBM.
- No more than one prior episode of progressive disease following previously received surgery and/or radiation and only one prior chemotherapy exposure of either temozolomide (TMZ) or nitrosourea including the application of polifeprosan (Gliadel®) wafers.
- Presence of measurable disease on gadolinium-enhanced magnetic resonance imaging (MRI).
- Patients taking steroids must have been on a stable dose for ≥ 7 days.
- Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2.
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- Hemoglobin ≥ 10 g/dL (or hematocrit > 29%), absolute neutrophil count (ANC) > 1500 cells/L, platelets > 100,000 cells/L.
- Serum creatinine < 1.5 mg/dL, blood urea nitrogen (BUN) < 25 mg/dL, serum aspartate aminotransferase (AST) and bilirubin < 1.5 x upper limit of normal (ULN).
- Sexually-active male and female patients were required to use double-barrier contraception (oral contraceptive plus barrier contraceptive) or must have undergone clinically documented total hysterectomy, ovariectomy, or tubal ligation.
- Female patients of childbearing potential must have had a negative pregnancy test within 48 hours prior to start of study drug.
- Life expectancy ≥ 8 weeks.
- Signed informed consent by the patient prior to patient entry and any study procedure.
Who cannot join
- Receipt of imatinib or hydroxyurea (HU) prior to study entry or receipt of any investigational agent within the last 6 months.
- Patients who had received a second course of chemotherapy or radiotherapy, unless given as a single localized application of radio surgery.
- In study STI571H2201 only, receipt of enzyme-inducing anticonvulsant drugs (EIACDs), eg, carbamazepine, phenobarbital, phenytoin, fosphenytoin, oxcarbazepine, or primidone. Previous EIACD should have been interrupted 4 weeks prior to study start.
- Grade ≥ 2 peripheral edema or pulmonary or pericardial effusions or ascites of any grade.
- Presence of any uncontrolled systemic infection.
- Patients who were not a minimum of 12 weeks from completion of conventional external beam radiotherapy unless:
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- There was new radiographical enhancement outside the field of radiation, or
- There was new pathological confirmation of recurrent tumor, or
- Progressive radiographical enhancement noted on post-radiotherapy/TMZ continue to worsen after an additional course of TMZ.
- Evidence of intra-tumor hemorrhage on pretreatment diagnostic imaging, except for stable post-operative Grade 1 hemorrhage, patients with an excessive risk of an intracranial hemorrhagic event, and patients with history of central nervous system (excluding post-operative Grade 1) or intraocular bleed.
- Patients who had undergone major surgery within 2 weeks prior to study entry or who had not recovered from prior major surgery, patients who had received chemotherapy within 4 weeks prior to study start, or who have not recovered from toxic effects of such therapy.
- Impairment of gastrointestinal function or gastrointestinal disease that could significantly alter the absorption of imatinib.
- Patients taking warfarin sodium.
- Known history of human immunodeficiency virus (HIV) seropositivity; testing for HIV was not required at study entry.
- For the purposes of MRI, patients with a pacemaker, ferromagnetic metal implants other than those approved as safe for use in MR scanners (eg, some types of aneurysm clips, shrapnel), patients suffering from uncontrollable claustrophobia, or those physically unable to fit into the machine (eg, obesity).
- Patients considered by the investigator as unlikely to be compliant with the study, take the study medications, travel for the necessary assessment visits, or have other medical conditions likely to interfere with the study assessments.
- Patients with another primary malignancy treated within the prior 3 years except excised squamous cell carcinomas of the skin and carcinoma in situ lesions of other organs which had been treated for cure.
- Patients not able to provide reliable informed consent and who did not have a legal representative for healthcare decisions on their behalf.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Phase II, Open-label, Multicenter Study Evaluating the Efficacy of Imatinib Plus Hydroxyurea (HU) in Patients With Progressive Glioblastoma Multiforme (GBM) Receiving or Not Receiving Enzyme-inducing Anticonvulsant Drugs (EIACDs)
This was an investigational study to assess the objective overall response (OOR) rate (complete response [CR] + partial response [PR]) of imatinib mesylate and hydroxyurea (hydroxycarbamide) combination therapy in patients with recurrent glioblastoma multiforme (brain tumors). This study also evaluated the duration of tumor response (as per MacDonald criteria), clinical benefit, progression-free survival rate at 6 and 12 months, and the survival rate at 12 and 24 months.
Read the detailed description
This ClinicalTrials.gov record includes the results from two studies (Novartis protocol IDs CSTI571H2201 and CSTI571H2202) which were conducted separately but reported together in a single clinical study report. Both studies were phase II, open-label, multicenter, single-arm studies that evaluated the efficacy of imatinib mesylate plus hydroxyurea in subjects with progressive glioblastoma multiforme. The studies were identical in design with two exceptions: Patients in study CSTI571H2201 received a dose of imatinib 600 mg once daily and were not allowed concomitant use of enzyme-inducing anticonvulsant drugs (EIACDs); patients in study CSTI571H2202 received a dose of imatinib 500 mg twice daily and were allowed concomitant use of EIACDs.
- Conditions
- Recurrent Glioblastoma Multiforme (GBM)
- Being tested
- Imatinib tablets, Hydroxyurea capsules
- Keywords
- imatinib mesylate, hydroxyurea, protein tyrosine kinases, glioma, glioblastoma multiforme, recurrent glioblastoma multiforme, GBM, MacDonald criteria
- Medical subject headings
- Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib tabletsDrug
Also called Glivec®
Imatinib was supplied as 100 and 400 mg tablets by Novartis.
Hydroxyurea capsulesDrug
Hydroxyurea was supplied locally as 500 mg capsules.
| Study group | Role | What they receive |
|---|---|---|
| Imatinib 600 mg + hydroxyurea 1000 mg | Experimental | Patients took imatinib 600 mg (1 imatinib 400 mg tablet and 2 imatinib 100 mg tablets) orally once daily with the morning meal. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were not allowed concomitant use of enzyme-inducing anticonvulsant drugs. Receives: Drug: Imatinib tablets; Drug: Hydroxyurea capsules |
| Imatinib 1000 mg + hydroxyurea 1000 mg | Experimental | Patients took imatinib 500 mg (1 imatinib 400 mg tablet and 1 imatinib 100 mg tablet) orally twice daily with the morning and evening meals. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were allowed concomitant use of enzyme-inducing anticonvulsant drugs. Receives: Drug: Imatinib tablets; Drug: Hydroxyurea capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients With an Objective Overall Response (OOR)
Patients with an OOR were those whose best response to treatment was a complete response (CR) or a partial response (PR) assessed with magnetic resonance imaging. A patient had a CR if the target tumors disappeared. A patient had a PR if there was a ≥ 50% reduction in the sum of the products of the largest perpendicular diameters of the target tumors compared to the baseline value. A best response of CR required at least 2 determinations of CR at least 4 weeks apart. A best response of PR required at least 2 determinations of PR or better at least 4 weeks apart (and not qualifying for CR).
Measured: Baseline to end of study (Month 24)
Secondary outcomes (5)
Duration of Objective Overall Response (OOR)
Duration of OOR only included patients whose best overall response was complete response (CR) or partial response (PR). The start date was the date of the first documented response (CR or PR); the end date was the date of the first documented disease progression (PD) or death from any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. If a patient had not progressed or died, the duration of OOR was censored at the time of the last OOR assessment.
Measured: Baseline to end of study (Month 24)
Percentage of Patients Who Had Clinical Benefit
Patients who had clinical benefit were patients with a best response of complete response (CR), partial response (PR), or stable disease (SD) lasting for more than 6 months from the start of treatment until the first documented disease progression (PD) or death from any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. SD was defined as insufficient tumor shrinkage to qualify for PR or CR and no increase in lesions which would qualify as PD.
Measured: Baseline to end of study (Month 24)
Percentage of Patients With Progression-free Survival at Months 6 and 12
Progression-free survival (PFS) was defined as the time from the start of treatment to the date of the first documented disease progression (PD) or death due to any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. If a patient had not progressed or died, progression-free survival was censored at the time of the last overall response assessment.
Measured: Months 6 and 12
Percentage of Patients Surviving at Months 6, 12, and 24
Patients not known to have died were censored at the time of last survival follow-up.
Measured: Months 6, 12, and 24
Number of Patients With at Least 1 Adverse Event
An adverse event (AE) is any undesirable sign, symptom, or medical condition occurring after starting study drug even if the event is not considered to be related to study drug. Study drug refers to imatinib or hydroxyurea. The study treatment is the combination of these two study drugs.
Measured: Baseline to end of study (Month 24)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2006 (estimated)
- Study startFeb 2006
- Primary completionAug 2008
- Study completionAug 2008
Why it stopped: Lack of efficacy
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 Recurrent Glioblastoma Multiforme (GBM)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 231 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- David Reardon, Dr., Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00290771
- Sponsor's protocol ID
- CSTI571H2201
- Other IDs
- CSTI571H2202
- Status last verified
- Apr 2011
- First submitted
- 10 Feb 2006
- Last updated
- 16 May 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open-label, Multicenter Study Evaluating the Efficacy of Imatinib Plus Hydroxyurea (HU) in Patients With Progressive Glioblastoma Multiforme (GBM) Receiving or Not Receiving Enzyme-inducing Anticonvulsant Drugs (EIACDs)
- ClinicalTrials.gov ID
- NCT00290771
- Acronym / sponsor ID
- CSTI571H2201
- Conditions
- Recurrent Glioblastoma Multiforme (GBM)
- Keywords
- imatinib mesylate, hydroxyurea, protein tyrosine kinases, glioma, glioblastoma multiforme, recurrent glioblastoma multiforme, GBM, MacDonald criteria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy
- Enrolment
- 231 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Feb 2006
- Primary completion
- Aug 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 13 Feb 2006 (estimated)
- Results
- Posted 16 May 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was an investigational study to assess the objective overall response (OOR) rate (complete response [CR] + partial response [PR]) of imatinib mesylate and hydroxyurea (hydroxycarbamide) combination therapy in patients with recurrent glioblastoma multiforme (brain tumors). This study also evaluated the duration of tumor response (as per MacDonald criteria), clinical benefit, progression-free survival rate at 6 and 12 months, and the survival rate at 12 and 24 months.
Detailed description
This ClinicalTrials.gov record includes the results from two studies (Novartis protocol IDs CSTI571H2201 and CSTI571H2202) which were conducted separately but reported together in a single clinical study report. Both studies were phase II, open-label, multicenter, single-arm studies that evaluated the efficacy of imatinib mesylate plus hydroxyurea in subjects with progressive glioblastoma multiforme. The studies were identical in design with two exceptions: Patients in study CSTI571H2201 received a dose of imatinib 600 mg once daily and were not allowed concomitant use of enzyme-inducing anticonvulsant drugs (EIACDs); patients in study CSTI571H2202 received a dose of imatinib 500 mg twice daily and were allowed concomitant use of EIACDs.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Imatinib 600 mg + hydroxyurea 1000 mg | Experimental | Drug: Imatinib tablets, Drug: Hydroxyurea capsulesPatients took imatinib 600 mg (1 imatinib 400 mg tablet and 2 imatinib 100 mg tablets) orally once daily with the morning meal. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were not allowed concomitant use of enzyme-inducing anticonvulsant drugs. |
| Imatinib 1000 mg + hydroxyurea 1000 mg | Experimental | Drug: Imatinib tablets, Drug: Hydroxyurea capsulesPatients took imatinib 500 mg (1 imatinib 400 mg tablet and 1 imatinib 100 mg tablet) orally twice daily with the morning and evening meals. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were allowed concomitant use of enzyme-inducing anticonvulsant drugs. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Males and females ≥ 18 years old.
- Histologically-confirmed diagnosis of progressive primary glioblastoma multiforme (GBM) based on original diagnosis. Patients with prior low-grade glioma were eligible if histological re-assessment demonstrated transformation to GBM.
- No more than one prior episode of progressive disease following previously received surgery and/or radiation and only one prior chemotherapy exposure of either temozolomide (TMZ) or nitrosourea including the application of polifeprosan (Gliadel®) wafers.
- Presence of measurable disease on gadolinium-enhanced magnetic resonance imaging (MRI).
- Patients taking steroids must have been on a stable dose for ≥ 7 days.
Key exclusion criteria (18 listed)
- Receipt of imatinib or hydroxyurea (HU) prior to study entry or receipt of any investigational agent within the last 6 months.
- Patients who had received a second course of chemotherapy or radiotherapy, unless given as a single localized application of radio surgery.
- In study STI571H2201 only, receipt of enzyme-inducing anticonvulsant drugs (EIACDs), eg, carbamazepine, phenobarbital, phenytoin, fosphenytoin, oxcarbazepine, or primidone. Previous EIACD should have been interrupted 4 weeks prior to study start.
- Grade ≥ 2 peripheral edema or pulmonary or pericardial effusions or ascites of any grade.
- Presence of any uncontrolled systemic infection.
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 tabletsAlso: Glivec®Imatinib was supplied as 100 and 400 mg tablets by Novartis. | Drug | Imatinib 1000 mg + hydroxyurea 1000 mg, Imatinib 600 mg + hydroxyurea 1000 mg |
| Hydroxyurea capsulesHydroxyurea was supplied locally as 500 mg capsules. | Drug | Imatinib 1000 mg + hydroxyurea 1000 mg, Imatinib 600 mg + hydroxyurea 1000 mg |
Primary outcome
Percentage of Patients With an Objective Overall Response (OOR)
Time frame: Baseline to end of study (Month 24)
Patients with an OOR were those whose best response to treatment was a complete response (CR) or a partial response (PR) assessed with magnetic resonance imaging. A patient had a CR if the target tumors disappeared. A patient had a PR if there was a ≥ 50% reduction in the sum of the products of the largest perpendicular diameters of the target tumors compared to the baseline value. A best response of CR required at least 2 determinations of CR at least 4 weeks apart. A best response of PR required at least 2 determinations of PR or better at least 4 weeks apart (and not qualifying for CR).
5 secondary outcomes
Duration of Objective Overall Response (OOR)
Time frame: Baseline to end of study (Month 24)
Percentage of Patients Who Had Clinical Benefit
Time frame: Baseline to end of study (Month 24)
Percentage of Patients With Progression-free Survival at Months 6 and 12
Time frame: Months 6 and 12
Percentage of Patients Surviving at Months 6, 12, and 24
Time frame: Months 6, 12, and 24
Number of Patients With at Least 1 Adverse Event
Time frame: Baseline to end of study (Month 24)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
David Reardon, Dr. principal investigator
Duke University
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 tablets and Hydroxyurea capsules in people with Recurrent Glioblastoma Multiforme (GBM), run by Novartis 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 12 inclusion and 18 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: stopped early, as of the sponsor's last update on 16 May 2011. 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 16 May 2011). 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?
Percentage of Patients With an Objective Overall Response (OOR) (time frame: Baseline to end of study (Month 24)). 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 16 May 2011.