Glioblastoma MultiformePhase 3NCT00154375
Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
A Phase 3 study testing Imatinib mesylate and Hydroxyurea in people with Glioblastoma Multiforme and Astrocytoma, run by Novartis Pharmaceuticals at 1 site in Germany.
Trial summary
This is a Phase III study comparing Imatinib mesylate and hydroxyurea combination therapy with hydroxyurea monotherapy in patients with temozolomide resistant progressive glioblastoma. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Glioblastoma Multiforme, Astrocytoma
- What is being tested?
- Imatinib mesylate and Hydroxyurea
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 1 siteGermany
- Study dates
- Oct 2004to Aug 2008
- Phase
- Phase 3
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent prior to initiation of any study procedure.
- Patients >= 18 years of age.
- Histological confirmed diagnosis of glioblastoma multiforme / astrocytoma World Health Organization (WHO) grade IV by a reference pathologist
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
- Adequate hepatic, renal and bone marrow function as defined by the following: total bilirubin < 1.5 x Upper Limit of Normal (ULN), ALT and AST < 2.5 x ULN, creatinine < 1.5 x ULN, absolute neutrophil count > 1.5 x109/L, platelets > 100 x109/L and hemoglobin > 10 g/dL.
- Female patients of childbearing potential with a negative pregnancy test within 7 days of initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential who agree to employ an effective barrier method of birth control throughout the study, and for up to 3 months following discontinuation of study drug.
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- Life expectancy of >3 months.
- MRI available every 6 weeks for disease management
- No intercerebral inflammation
- Irradiation therapy 54 to 62 gy finished or less according to national standard
- Chemotherapy at least 1 temozolomide containing regimen finished, no established chemotherapy regiment available and progression under chemotherapy or in between 6 months following the last chemotherapy.
- Leucocytes > 2.500/µl, to be controlled once a week
- Thrombocytes > 80.000/µl, to be controlled once a week
- Ensured compliance
- Patients who had a second or third resection after disease progression cannot be included earlier than 2 weeks following the resection. MRI should be performed not later than 72 h post operation. If patients are to be included later than 4 weeks after the resection, a new baseline MRI must be performed.
Who cannot join
- Female patients who are pregnant or breast-feeding.
- Patients who have been treated with any investigational agent(s) within 28 days of the first day of administration of study drug.
- Patients with uncontrolled medical disease such as diabetes mellitus, thyroid dysfunction, neuropsychiatric disorders, infection, angina or Grade 3 or 4 cardiac problems as defined by the New York Heart Association Criteria.
- Patients with other malignant disorders.
- Patient with acute or known chronic liver disease (i.e., chronic active hepatitis, cirrhosis).
- Patients who are known to be HIV positive (no specific tests are required for confirmation of eligibility).
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- Expected incompliance according to treatment, treatment diary and examination schedule
- Not confirmed histological diagnosis glioblastoma multiforme/astrocytoma WHO grade IV
- Other drugs with potential cytostatic main or side effect
- No or inadequate chemotherapy or irradiation therapy
- Patients without hematological recovery after previous chemotherapy who have been treated with Chemotherapy within 28 days of the first day of administration of study drug.
- Other protocol-specific inclusion /exclusion criteria may apply.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase III Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
This is a Phase III study comparing Imatinib mesylate and hydroxyurea combination therapy with hydroxyurea monotherapy in patients with temozolomide resistant progressive glioblastoma.
- Conditions
- Glioblastoma Multiforme, Astrocytoma
- Being tested
- Imatinib mesylate, Hydroxyurea
- Keywords
- Open label, Imatinib mesylate, hydroxyurea, temozolomide, resistant, protein tyrosine kinases, adenocarcinoma, glioblastoma multiforme, astrocytoma, brain tumor, brain cancer
- Medical subject headings
- Glioblastoma, Astrocytoma, Adenocarcinoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib mesylateDrug
Also called Glivec®
Imatinib was supplied as 100 mg and 400 mg tablets packaged in polyethylene bottles.
HydroxyureaDrug
Also called Litalir®
| Study group | Role | What they receive |
|---|---|---|
| Imatinib mesylate + hydroxyurea (HU) | Experimental | Imatinib was supplied as 100 mg and 400 mg tablets. Patients in the combination arm were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time). Every 6 weeks after randomization based on assessment of therapeutic response, either patients continued with above mentioned dosing regimen or switched to receive a daily dose of 800 mg imatinib with 1000 mg HU. Patients were instructed to split the intake, taking 400 mg imatinib with 500 mg HU in the morning, then the same in the evening. Receives: Drug: Imatinib mesylate; Drug: Hydroxyurea |
| Hydroxyurea alone | Active comparator | 1500 mg/day of HU given as 500 mg 3 times daily. Every 6 weeks after randomization and based on assessment of therapeutic response, the patients were either switched to combination arm or continued in monotherapy arm of hydroxyurea. Receives: Drug: Hydroxyurea |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Progression Free Survival (PFS) During the Study Duration
PFS was defined as the time from the date of randomization to the date of the first documented progression according to the MacDonald criteria, or death due to any cause. MacDonald criteria are standard criteria in neurooncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).
Measured: 6 months -1 year
Secondary outcomes (1)
Number of Participants With Death, Other Serious or Clinically Significant Adverse Events (AEs) or Related Discontinuations
National Cancer Institute (NCI)/ National Institute of Health (NIH) provides a grading (severity) scale for each AE term. Grade 3 refers to severe AE and Grade 4 refers to life-threatening or disabling AE. According to FDA 21CFR 314.80, a serious adverse event (SAE) is described as any adverse event that leads to death, is life threatening ( NIH criteria Grade 4), causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.
Measured: 6 months - 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startOct 2004
- Primary completionAug 2008
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 Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 240 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00154375
- Sponsor's protocol ID
- CSTI571BDE40
- Status last verified
- Apr 2011
- First submitted
- 9 Sep 2005
- Last updated
- 26 Apr 2011
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
- ClinicalTrials.gov ID
- NCT00154375
- Acronym / sponsor ID
- CSTI571BDE40
- Conditions
- Glioblastoma Multiforme, Astrocytoma
- Keywords
- Open label, Imatinib mesylate, hydroxyurea, temozolomide, resistant, protein tyrosine kinases, adenocarcinoma, glioblastoma multiforme
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 240 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2004
- Primary completion
- Aug 2008 (actual)
- First posted
- 12 Sep 2005 (estimated)
- Results
- Posted 2 Feb 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase III study comparing Imatinib mesylate and hydroxyurea combination therapy with hydroxyurea monotherapy in patients with temozolomide resistant progressive glioblastoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Imatinib mesylate + hydroxyurea (HU) | Experimental | Drug: Imatinib mesylate, Drug: HydroxyureaImatinib was supplied as 100 mg and 400 mg tablets. Patients in the combination arm were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time). Every 6 weeks after randomization based on assessment of therapeutic response, either patients continued with above mentioned dosing regimen or switched to receive a daily dose of 800 mg imatinib with 1000 mg HU. Patients were instructed to split the intake, taking 400 mg imatinib with 500 mg HU in the morning, then the same in the evening. |
| Hydroxyurea alone | Active comparator | Drug: Hydroxyurea1500 mg/day of HU given as 500 mg 3 times daily. Every 6 weeks after randomization and based on assessment of therapeutic response, the patients were either switched to combination arm or continued in monotherapy arm of hydroxyurea. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Signed informed consent prior to initiation of any study procedure.
- Patients >= 18 years of age.
- Histological confirmed diagnosis of glioblastoma multiforme / astrocytoma World Health Organization (WHO) grade IV by a reference pathologist
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
- Adequate hepatic, renal and bone marrow function as defined by the following: total bilirubin < 1.5 x Upper Limit of Normal (ULN), ALT and AST < 2.5 x ULN, creatinine < 1.5 x ULN, absolute neutrophil count > 1.5 x109/L, platelets > 100 x109/L and hemoglobin > 10 g/dL.
Key exclusion criteria (12 listed)
- Female patients who are pregnant or breast-feeding.
- Patients who have been treated with any investigational agent(s) within 28 days of the first day of administration of study drug.
- Patients with uncontrolled medical disease such as diabetes mellitus, thyroid dysfunction, neuropsychiatric disorders, infection, angina or Grade 3 or 4 cardiac problems as defined by the New York Heart Association Criteria.
- Patients with other malignant disorders.
- Patient with acute or known chronic liver disease (i.e., chronic active hepatitis, cirrhosis).
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 mesylateAlso: Glivec®Imatinib was supplied as 100 mg and 400 mg tablets packaged in polyethylene bottles. | Drug | Imatinib mesylate + hydroxyurea (HU) |
| HydroxyureaAlso: Litalir® | Drug | Hydroxyurea alone, Imatinib mesylate + hydroxyurea (HU) |
Primary outcome
Percentage of Participants With Progression Free Survival (PFS) During the Study Duration
Time frame: 6 months -1 year
PFS was defined as the time from the date of randomization to the date of the first documented progression according to the MacDonald criteria, or death due to any cause. MacDonald criteria are standard criteria in neurooncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).
1 secondary outcome
Number of Participants With Death, Other Serious or Clinically Significant Adverse Events (AEs) or Related Discontinuations
Time frame: 6 months - 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Imatinib mesylate and Hydroxyurea in people with Glioblastoma Multiforme and Astrocytoma, run by Novartis Pharmaceuticals at 1 site in Germany.
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 15 inclusion and 12 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 26 Apr 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 Germany. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 2 Feb 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 Participants With Progression Free Survival (PFS) During the Study Duration (time frame: 6 months -1 year). 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 26 Apr 2011.