This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma (NCT00154375), a randomized phase 3 study. The primary outcome is Percentage of Participants With Progression Free Survival (PFS) During the Study Duration.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00154375 |
| Phase | Phase 3 |
| Condition | Glioblastoma Multiforme, Astrocytoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 240 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Patients with temozolomide-resistant progressive glioblastoma were eligible for the trial. The registry record also lists glioblastoma multiforme and astrocytoma as conditions. The primary-outcome description defines the intention-to-treat population as all randomized patients, analyzed according to their randomized treatment.
Intervention
The combination regimen used oral imatinib mesylate with hydroxyurea. The reported daily doses were 600 mg of imatinib and 1000 mg of hydroxyurea. The registry record says patients were instructed to take imatinib at lunch and hydroxyurea twice daily.
Comparator
The comparator was hydroxyurea alone, reported as 1500 mg per day, given as 500 mg three times daily. The registry record describes response-based assessment every 6 weeks and says patients in this arm could either switch to combination treatment or continue hydroxyurea monotherapy.
Primary question
The primary outcome was the percentage of participants with progression-free survival during the study duration, with a stated timeframe of 6 months -1 year. The registry record does not report the arm-level percentages, their confidence intervals, or a treatment-effect estimate, so the magnitude and precision of any between-group difference cannot be assessed from the posted results.
3. Trial Design
This was a Phase III, randomized, parallel-group trial with no masking. The registry record lists enrollment of 240 participants, a start date of 2004-10, primary completion in 2008-08, and a status of completed. The sponsor was Novartis Pharmaceuticals. The trial compared an imatinib mesylate and hydroxyurea combination with hydroxyurea alone in people with temozolomide-resistant progressive glioblastoma.
Randomization is intended to make treatment groups comparable, on average, at the point of assignment. A parallel-group design assigns participants to treatment groups for comparison rather than having every participant receive each treatment in a planned sequence. No masking means participants and study personnel were not blinded to assignment, according to the registry record. Details about allocation concealment, randomization procedures, or stratification are not reported in the registry record.
The treatment descriptions include response-based changes after randomization. In the hydroxyurea-alone arm, assessment every 6 weeks could lead either to a switch to combination treatment or to continuation of hydroxyurea. The combination-arm description also refers to assessments every 6 weeks, but the registry text is truncated before the full description is completed. The timing and rules for changes in treatment therefore cannot be fully reconstructed from the record.
Because treatment could change after assignment, an intention-to-treat comparison would preserve the original randomized groups and estimate the effect of assignment to each treatment strategy, including subsequent changes. The primary-outcome description defines the intention-to-treat population as all randomized patients analyzed according to randomized treatment. The record does not report the number analyzed in each randomized group or details of adherence and treatment received over time.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Imatinib Mesylate + Hydroxyurea (HU) | Hydroxyurea Alone |
|---|---|---|
| STARTED | 120 | 120 |
| Discontinued Study Treatment | 111 | 104 |
| Not Exposed to Study Treatment | 2 | 2 |
| COMPLETED | 7 | 14 |
| NOT COMPLETED | 113 | 106 |
Reasons for not completing this period:
| Reason | Imatinib Mesylate + Hydroxyurea (HU) | Hydroxyurea Alone |
|---|---|---|
| Unsatisfactory therapeutic effect | 25 | 26 |
| Adverse Event | 18 | 20 |
| Withdrawal by Subject | 14 | 10 |
| Death | 5 | 13 |
| Study drug no longer required | 5 | 3 |
| Lost to Follow-up | 2 | 1 |
| Abnormal laboratory value(s) | 0 | 2 |
| Protocol Violation | 0 | 1 |
| Suspected progression of disease | 44 | 30 |
Analysis population for the primary outcome, as defined in the registry: The ITT population consists of all randomized patients, analyzed according to their randomized treatment.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Imatinib Mesylate + Hydroxyurea (HU) | Hydroxyurea Alone | Total |
|---|---|---|---|---|
| Participants analysed | 120 | 120 | 240 | |
| Age Continuous | years | 52.1 (SD 11.3) | 50.2 (SD 11.4) | 51.2 (SD 11.4) |
| Sex: Female, Male: Female | Participants | 50 | 38 | 88 |
| Sex: Female, Male: Male | Participants | 70 | 82 | 152 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Progression Free Survival (PFS) During the Study Duration, measured over 6 months -1 year.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage of Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with progression-free survival during the stated timeframe of 6 months -1 year. Progression-free survival was defined as the time from randomization to the first documented progression under the MacDonald criteria, or death from any cause. It combines disease progression and death into an event definition, so a participant is not counted as progression-free after either event.
Tumor assessment used an adapted version of the MacDonald criteria. The registry describes a combined evaluation of MRI findings, including measurable, evaluable, and new lesions; neurological performance; and concomitant steroid use. MRI assessment was also made by an independent external expert. Neurological performance and steroid use were reported by the investigator.
A percentage with progression-free survival can communicate the proportion meeting the endpoint at a specified period, while the underlying endpoint definition concerns time until progression or death. Those are related but not identical forms of reporting: an estimate at a particular time does not by itself describe the full distribution of event times. The registry record does not report the actual percentages, confidence intervals, or detailed analysis method, so neither the endpoint estimates nor their precision can be evaluated from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record identifies progression-free survival as the primary outcome, but it does not report the outcome values by treatment group. It also does not report a treatment-effect estimate, confidence intervals, or a statistical test for the primary comparison. As a result, the registry record does not establish the direction, size, or precision of a difference between the randomized strategies. The endpoint definition and planned timeframe explain what was to be measured, but they are not outcome findings.
The listed enrollment is 240. Enrollment alone does not show how many participants contributed to a particular endpoint estimate, how many experienced progression or death, or how many had incomplete follow-up. Group-specific analysis counts and event counts for progression-free survival are not reported in the registry record. Those details would be needed to understand the information underlying an estimate, alongside the estimate and its uncertainty.
The endpoint includes progression or death and uses MRI, neurological performance, and steroid use in its progression assessment. This makes the result dependent on the stated assessment criteria and the completeness and timing of assessments. The record notes external expert assessment of MRI scans, but does not describe adjudication procedures, assessment schedules in full, or handling of disagreements. These details are not reported in the registry record.
Post-randomization treatment changes are also relevant to interpretation. The hydroxyurea-alone group could continue monotherapy or switch to combination treatment after response assessment every 6 weeks. Such changes may make a comparison of treatment received differ from a comparison based on randomized assignment. The primary-outcome definition specifies an intention-to-treat population, but the record does not provide the analysis results or enough detail to determine how treatment changes were incorporated in the reported analyses.
The adverse-event figures describe affected participants across treatment periods, but they do not substitute for the primary efficacy outcome. The periods include hydroxyurea alone and a period after switching to combination treatment, with different numbers at risk in those groups. Those figures should not be treated as a randomized comparison of the initial strategies without further information about follow-up, exposure, and analysis.
Overall, the available record supports a description of the trial question and its endpoint, not a conclusion about comparative efficacy. No primary-outcome result or statistical analysis is listed. The absence of a posted estimate means the clinical size and statistical precision of the intended comparison cannot be judged from this record.
9. Statistical Methods Explained
The record describes a randomized parallel-group trial and defines the primary outcome as a percentage of participants with progression-free survival. It does not report the analysis method used to produce that outcome, a treatment-effect estimate, or a statistical test. The concepts below explain how such statistics are generally interpreted; they do not identify methods that this trial necessarily used.
What does randomization contribute?
In general, randomization assigns participants to treatment groups through a chance-based process. It can reduce systematic differences between groups at baseline, though it does not guarantee that every prognostic characteristic will be balanced in a particular trial. A valid comparison also depends on follow-up and analysis choices after assignment. The registry record does not describe the randomization sequence, concealment procedures, or any stratification factors.
What does intention-to-treat mean?
In general, an intention-to-treat analysis keeps participants in the groups to which they were randomized, regardless of whether they later stop, switch, or otherwise change treatment. This approach preserves the original randomized comparison and is particularly relevant when treatment changes occur after assignment. The registry defines its intention-to-treat population as all randomized patients analyzed according to randomized treatment. It does not report how many participants were included in each analysis or whether every randomized participant had usable outcome data.
How should a percentage be interpreted?
The primary outcome is described as the percentage of participants with progression-free survival. A percentage gives a proportion for the outcome definition and reporting period, but it needs context: the number of participants analyzed, the time point or interval, the event definition, and an uncertainty estimate. A confidence interval is a range calculated by a statistical method to express the precision of an estimate. In general, a wider interval indicates less precision than a narrower interval. The endpoint record specifies a 95% confidence interval as the dispersion measure, but actual interval values are not reported in the registry record.
Progression-free survival is defined using time from randomization to progression or death. In general, time-to-event analyses can account for different lengths of follow-up and for participants whose event has not been observed by the end of available follow-up. Such methods require rules for censoring and assumptions about the relationship between censoring and the event process. Those rules and the analysis method are not reported in the registry record. A percentage at a specified period and a time-to-event summary answer related but distinct questions, and the available record does not clarify how the stated percentage was estimated.
Why do assessment criteria matter?
The progression definition uses adapted MacDonald criteria and combines MRI evaluation, neurological performance, and steroid use. In general, a composite assessment can incorporate more than one aspect of disease status, but interpretation depends on the prespecified definitions, assessment schedule, and consistency of measurement. The registry notes independent external expert assessment of MRI findings, but does not give the full process for review or resolution of differences. The primary endpoint therefore has a stated definition, while important operational details are not reported in the registry record.
What do the planning illustrations represent?
The record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are illustrations based on the observed effect, not the trial's own design assumptions or observed power. In general, sample-size calculations estimate the number of participants needed under specified assumptions; they do not establish that the trial had a particular probability of detecting its observed result. No numerical illustration values are reported in the registry record, and the original sample-size justification is not reported in the registry record.
When outcomes are counts or percentages, over-dispersion can matter in settings where variability is greater than a simple statistical model assumes. In general, accounting for over-dispersion can change uncertainty estimates and tests. The record does not identify an over-dispersion model for the primary endpoint, and it would be inappropriate to infer that one was used.
Finally, interpretation of any confidence interval or test would depend on the analysis population, missing-data handling, and whether multiple outcomes or comparisons were addressed. The registry record lists no analyses and does not report these details. Statistical methods should therefore be read as general principles rather than as a description of unreported trial procedures.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 2 outcome measures and identifies progression-free survival as the primary outcome. It also lists a secondary outcome concerning participants with death, other serious or clinically significant adverse events, or related discontinuations. No analyses are listed. The record does not report whether the primary endpoint included multiple planned time points or comparisons, whether multiplicity was controlled, or whether any hierarchy of hypotheses was specified. A multiplicity strategy is not reported in the registry record.
Multiplicity matters in general when several outcomes, time points, or comparisons are tested. The more results examined, the greater the opportunity for chance findings if each is interpreted separately without an appropriate strategy. This is a general statistical consideration, not evidence that the trial conducted a particular set of tests. The primary outcome's stated timeframe spans 6 months -1 year, but the registry record does not give arm-level estimates or explain how that timeframe was handled analytically.
The primary-outcome description defines the intention-to-treat population as all randomized patients analyzed according to randomized treatment. That definition clarifies the intended population, but does not describe the handling of missing outcome data. Methods for incomplete follow-up, missing MRI or clinical assessments, censoring, and sensitivity analyses are not reported in the registry record.
Because participants in the hydroxyurea-alone group could switch treatment after response assessment, analysis choices concerning post-randomization treatment are important. The record states the intention-to-treat population definition but does not report how switches, protocol deviations, or treatment discontinuations were handled in the analysis. These omissions limit the ability to assess the robustness of any treatment comparison; no efficacy analysis is posted in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Imatinib Mesylate + Hydroxyurea (HU) | 64 | 118 | 54.2% |
| Period With Hydroxyurea Alone | 46 | 118 | 39.0% |
| Period After Switch to Combination | 49 | 85 | 57.6% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Imatinib Mesylate + Hydroxyurea (HU) | 104 of 118 |
| Period With Hydroxyurea Alone | 80 of 118 |
| Period After Switch to Combination | 65 of 85 |
Most frequent serious adverse event terms
| Event term | Organ system | Imatinib Mesylate + Hydroxyurea (HU) | Period With Hydroxyurea Alone | Period After Switch to Combination |
|---|---|---|---|---|
| EPILEPSY | Nervous system disorders | 5 of 118 | 9 of 118 | 9 of 85 |
| PNEUMONIA | Infections and infestations | 9 of 118 | 4 of 118 | 5 of 85 |
| GENERAL PHYSICAL HEALTH DETERIORATION | General disorders | 7 of 118 | 6 of 118 | 2 of 85 |
| HEMIPARESIS | Nervous system disorders | 8 of 118 | 5 of 118 | 2 of 85 |
| CONVULSION | Nervous system disorders | 3 of 118 | 4 of 118 | 4 of 85 |
| HEADACHE | Nervous system disorders | 2 of 118 | 5 of 118 | 3 of 85 |
| INTRACRANIAL PRESSURE INCREASED | Nervous system disorders | 3 of 118 | 3 of 118 | 4 of 85 |
| LEUKOPENIA | Blood and lymphatic system disorders | 1 of 118 | 2 of 118 | 5 of 85 |
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | 3 of 118 | 3 of 118 | 2 of 85 |
| FALL | Injury, poisoning and procedural complications | 3 of 118 | 1 of 118 | 3 of 85 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Imatinib Mesylate + Hydroxyurea (HU) | Period With Hydroxyurea Alone | Period After Switch to Combination |
|---|---|---|---|---|
| FATIGUE | General disorders | 34 of 118 | 16 of 118 | 18 of 85 |
| HEADACHE | Nervous system disorders | 26 of 118 | 24 of 118 | 16 of 85 |
| THROMBOCYTOPENIA | Blood and lymphatic system disorders | 24 of 118 | 15 of 118 | 17 of 85 |
| NAUSEA | Gastrointestinal disorders | 28 of 118 | 17 of 118 | 10 of 85 |
| OEDEMA PERIPHERAL | General disorders | 29 of 118 | 12 of 118 | 14 of 85 |
| LEUKOPENIA | Blood and lymphatic system disorders | 16 of 118 | 14 of 118 | 14 of 85 |
| VOMITING | Gastrointestinal disorders | 21 of 118 | 13 of 118 | 6 of 85 |
| ANAEMIA | Blood and lymphatic system disorders | 13 of 118 | 8 of 118 | 13 of 85 |
| ASTHENIA | General disorders | 11 of 118 | 6 of 118 | 9 of 85 |
| DIZZINESS | Nervous system disorders | 16 of 118 | 3 of 118 | 7 of 85 |
Serious events with the highest arm-level rate: epilepsy (10.6%), pneumonia (7.6%), hemiparesis (6.8%), general physical health deterioration (5.9%), leukopenia (5.9%).
The registry lists serious adverse-event counts for three treatment periods. In the imatinib mesylate plus hydroxyurea group, 64 participants were affected out of 118 at risk. In the period with hydroxyurea alone, 46 were affected out of 118 at risk. In the period after switching to combination treatment, 49 were affected out of 85 at risk. The listed counts for other adverse events are 104 out of 118, 80 out of 118, and 65 out of 85, respectively. These are counts of participants affected, not rates calculated.
The treatment periods are not interchangeable randomized groups: one is a period after switching, and its number at risk differs from the other periods. The registry record does not report exposure duration, event timing, or a method for comparing these periods. The listed serious-event terms include epilepsy at 10.6%, pneumonia at 7.6%, hemiparesis at 6.8%, general physical health deterioration at 5.9%, leukopenia at 5.9%, and convulsion at 4.7%. Death counts are not reported in the registry record. These safety figures should be read as descriptive registry entries, not as a direct estimate of comparative treatment risk.
12. What the Result Does, and Does Not, Mean
The trial record describes a randomized comparison of imatinib mesylate plus hydroxyurea with hydroxyurea alone in temozolomide-resistant progressive glioblastoma. It defines progression-free survival as the primary outcome and describes how progression was assessed. It also records adverse-event counts across treatment periods. These registry entries identify the clinical question and the outcomes recorded, but they do not establish what the primary comparison found.
The registry record does not report the arm-level progression-free survival percentages, confidence intervals, or a comparative treatment estimate. Without those values, the size and direction of any difference cannot be determined, and its precision cannot be assessed. The trial's completed status and enrollment of 240 do not, by themselves, establish a treatment effect or explain the uncertainty around one.
Even if outcome estimates were available, they would need to be interpreted with their definitions and analysis context. Progression-free survival includes progression or death, and progression assessment combined MRI findings, neurological performance, and steroid use. Treatment switching after randomization is also part of the recorded study context. An intention-to-treat analysis would address the randomized treatment strategies, while a comparison based on treatment actually received would pose a different question.
The safety counts likewise have limitations as comparative evidence. They are reported across periods with different treatment descriptions and numbers at risk; the registry record does not provide the follow-up and exposure details needed to interpret them as a direct comparison of randomized strategies. The listed adverse-event percentages are descriptive entries and do not answer the primary efficacy question.
Accordingly, the posted information supports a careful description of the design, endpoint, and adverse-event reporting, but not a conclusion that one treatment strategy had better or worse progression-free survival. No medical recommendation follows from the information in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable for the combination of a randomized treatment assignment and post-randomization treatment switching. Randomization creates the basis for comparing assigned strategies, while switching can make the treatment actually received differ from the treatment initially assigned. The distinction matters because an intention-to-treat analysis and an analysis based on treatment received target different questions. The registry defines an intention-to-treat population but does not report the analysis results or detailed handling of switches.
The primary endpoint also illustrates the importance of clear outcome definitions. Progression-free survival includes both documented progression and death, and progression is assessed using MRI findings, neurological performance, and steroid use. The registry describes an independent external expert assessment of MRI scans. These elements help explain what the endpoint represents, while the absent analysis details leave uncertainty about assessment timing and implementation.
Another important statistical point is the difference between a defined outcome and a reported result. The record provides the endpoint and states that a 95% confidence interval was the dispersion measure, but it does not post the arm-level estimates or intervals. Without them, readers cannot judge the magnitude or precision of the primary comparison. A completed trial and a listed enrollment do not replace those results.
The adverse-event entries also show why denominators and treatment periods matter. Counts are presented for the combination group, hydroxyurea-alone period, and period after switching to combination, with different numbers at risk. A simple comparison across these periods would not automatically preserve the randomized design or account for differences in exposure and follow-up. The record does not report a comparative safety analysis.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most important limitation of the registry record for statistical interpretation is that it does not report primary-outcome results. Arm-level progression-free survival estimates, confidence intervals, event counts, and a treatment comparison are not reported in the registry record. Consequently, the effect's direction, magnitude, and precision cannot be assessed.
The endpoint is specified as a percentage over a timeframe of 6 months -1 year, but the record does not explain how that interval was translated into a particular analysis or estimate. The exact assessment schedule, censoring rules, and analysis method are not reported in the registry record. The definition of progression includes several assessment components, but details about adjudication and the handling of incomplete or conflicting assessments are not reported.
Switching after randomization complicates interpretation. The hydroxyurea-alone arm could continue monotherapy or move to combination treatment after response assessment every 6 weeks. The combination-arm description is truncated, and full treatment-change rules are not reported in the registry record. Although the endpoint description defines an intention-to-treat population, analysis details concerning switches, discontinuations, and adherence are not reported.
There is no listed analysis, and methods for missing data, multiplicity, or sensitivity analyses are not reported in the registry record. The original sample-size justification is also not reported. The serious and other adverse-event counts are divided by treatment period, but exposure duration and comparative analysis methods are not reported. These limitations constrain interpretation of both efficacy and safety from the registry information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma — NCT00154375.
- Registry record last updated 2011-04-26; status last verified 2011-04.
- Results first posted 2011-02-02.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00154375 is a completed, randomized, unmasked Phase III parallel-group trial sponsored by Novartis Pharmaceuticals. It enrolled 240 participants and compared imatinib mesylate plus hydroxyurea with hydroxyurea alone in temozolomide-resistant progressive glioblastoma. The registry lists a start date of 2004-10 and primary completion in 2008-08.
The primary outcome was the percentage of participants with progression-free survival, defined by progression under adapted MacDonald criteria or death. The record describes MRI, neurological performance, and steroid use as assessment components and defines the intention-to-treat population as all randomized patients analyzed according to assignment. Arm-level primary-outcome results and analyses are not reported in the registry record. Adverse-event counts are listed across treatment periods, including a period after switching to combination treatment, but a comparative safety analysis is not reported.