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 Bosutinib in Adult Patients With Recurrent Glioblastoma (NCT01331291), a non-randomized phase 2 study. The primary outcome is Progression-Free Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01331291 |
| Phase | Phase 2 |
| Condition | Glioblastoma |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 36 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Adults with recurrent glioblastoma were eligible for this Phase 2 trial. The primary outcome description focuses on patients at first or second recurrence who entered Arm B. The overall enrollment was 36, but the number enrolled in Arm B is not reported in the registry record.
Intervention
The intervention was oral bosutinib. Arm A included patients who were surgical candidates and received bosutinib before resection, with dosing resumed after at least 10 days elapsed post-operatively. Arm B included patients who were not surgical candidates and received daily bosutinib in 28 day cycles.
Comparator
The registry describes a non-randomized, parallel-arm study with no masking. Arm A and Arm B were distinguished by surgical candidacy and treatment pathway, rather than by assignment to bosutinib versus a control treatment. The record does not describe a like-for-like control comparison.
Primary question
The primary outcome was progression-free survival for Arm B, measured from initiation of study treatment to date of progression. The outcome description says progression-free survival was to be assessed at six months; the registry timeframe is listed as 2 years. The median and its 95% confidence interval are not reported in the registry record.
3. Trial Design
This was a completed Phase 2 trial of bosutinib in adults with recurrent glioblastoma, sponsored by Massachusetts General Hospital. The registry records enrollment of 36 and describes the study as open label, non-randomized, unmasked, and parallel-arm. Those design features mean that treatment assignment was not randomized and participants and study personnel were not masked to treatment.
The arms reflected different clinical pathways. Arm A consisted of patients who were surgical candidates. They received oral bosutinib at 400mg daily for 7-9 days before resection; dosing resumed after at least 10 days elapsed post-operatively. Arm B consisted of patients who were not surgical candidates. They received oral bosutinib at 400 mg daily in 28 day cycles until disease progression, intolerability, or withdrawal of consent.
The primary outcome applied only to Arm B. Its stated population was patients with recurrent glioblastoma at first or second recurrence receiving continuous daily bosutinib. The listed outcome was progression-free survival, measured from treatment initiation to progression. Although the timeframe field says 2 years, the outcome description specifically mentions assessment at six months.
The registry lists intratumoral concentration, safety profile, and anti-tumor response as secondary outcomes. It records four outcome measures, but no analysis entries. The statistical analysis plan, sample-size justification, interim analysis plan, and detailed analysis populations are not reported in the registry record. Because Arm A and Arm B differed by surgical candidacy and treatment pathway, their outcomes should not be treated as a randomized comparison.
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 | Arm A | Arm B |
|---|---|---|
| STARTED | 2 | 9 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 2 | 9 |
Reasons for not completing this period:
| Reason | Arm A | Arm B |
|---|---|---|
| Lack of Efficacy | 2 | 8 |
| Death | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: This outcome was only applicable to participants enrolled on Arm B.
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 | Arm A | Arm B | Total |
|---|---|---|---|---|
| Participants analysed | 2 | 9 | 11 | |
| Age, Continuous | years | 60 (58 to 62) | 44 (36 to 62) | 52 (36 to 62) |
| Sex: Female, Male: Female | Participants | 0 | 4 | 4 |
| Sex: Female, Male: Male | Participants | 2 | 5 | 7 |
| Prior Surgery: Gross Total Resection | participants | 1 | 6 | 7 |
| Prior Surgery: Sub total Resection | participants | 0 | 3 | 3 |
| Prior Surgery: No prior surgery | participants | 1 | 0 | 1 |
| Karnofsky Performance Status (KPS) | units on a scale | 80 (70 to 90) | 90 (70 to 90) | 90 (70 to 90) |
| Prior chemoradiation | participants | 2 | 9 | 11 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-Free Survival, measured over 2 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | weeks |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival is a time-to-event outcome: it measures the time from a defined starting point until disease progression. In this trial, the registry defines the start as initiation of study treatment and the event as the date of progression. The primary outcome was specific to Arm B, rather than applying to all enrolled participants.
The registry describes an assessment at six months in patients with recurrent glioblastoma at first or second recurrence who received continuous daily dosing. It also lists a timeframe of 2 years. These descriptions are both part of the record; it does not clarify how the listed timeframe relates to the six-month assessment.
General statistical context. Time-to-event outcomes can account for differing follow-up durations and for participants whose event has not been observed by the end of their available follow-up. A median is the time by which half of the relevant population has experienced the event, as estimated by the analysis. A confidence interval communicates uncertainty around that estimate. The median progression-free survival and its 95% confidence interval are not reported in the registry record, so the endpoint's magnitude and precision cannot be assessed 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 a median estimate or a 95% confidence interval. It also contains no analysis entries. Consequently, the primary outcome's observed value, its precision, and the statistical evidence associated with it are not reported in the registry record. The design and outcome definition alone cannot establish how long participants remained progression-free.
The primary outcome applies only to Arm B. The overall enrollment was 36, but the number contributing to the primary outcome is not reported in the registry record. The two arms were formed according to surgical candidacy, and Arm A had a perioperative treatment schedule while Arm B received ongoing dosing. Their outcomes therefore do not provide a randomized comparison of bosutinib with a control treatment or a direct estimate of a treatment effect.
The record lists intratumoral concentration, safety profile, and anti-tumor response as secondary outcomes, but gives no detailed numerical results for those outcomes in the registry entries. The record does list adverse-event figures for a combined-arms group. Those figures describe reported safety observations and should not be interpreted as evidence about progression-free survival or tumor response.
General statistical context. A point estimate is most informative when read together with its uncertainty interval and the amount of follow-up and event information supporting it. A narrow confidence interval generally indicates greater precision than a wide one, while neither interval width nor an estimate alone resolves possible bias in study design. Since the primary estimate and interval are absent, no assessment of precision is possible.
The registry labels the trial completed, with primary completion recorded as 2014-12. Completion status does not itself supply an outcome result. The available record therefore supports a description of the trial design, outcome definition, and selected adverse-event counts, but not a quantitative conclusion about the primary progression-free survival outcome.
9. Statistical Methods Explained
What kind of outcome is progression-free survival?
General statistical context. Progression-free survival is a time-to-event measure. Each participant contributes follow-up from the defined starting point until progression is observed or until follow-up ends without a recorded progression. The latter situation is commonly described as censoring. Censoring does not mean that progression did not happen; it means the event time is not known within the available observation period.
For this trial, the registry specifies treatment initiation as the start and date of progression as the event. It names a median as the outcome parameter and a 95% confidence interval as the dispersion measure. However, neither the median nor the confidence interval is reported in the registry record. The record also does not report the number of progression events, the censoring details, or the follow-up distribution.
What does a confidence interval communicate?
General statistical context. A confidence interval expresses the statistical uncertainty associated with an estimate under the assumptions of the analysis. It is not a guarantee that the true value lies within the particular interval, and it does not correct for bias caused by non-randomized assignment, outcome measurement, or incomplete follow-up. Interpreting an interval requires both its endpoints and an understanding of the population and method used to calculate it.
The registry names a 95% confidence interval for the median progression-free survival, but does not post its endpoints. As a result, neither the estimated range nor the interval's width can be assessed. No hazard ratio is reported in the registry record, and no analysis entries are listed.
Why does the trial structure matter?
General statistical context. Randomization tends to balance measured and unmeasured baseline characteristics between comparison groups, on average. In a non-randomized study, groups can differ for reasons related to treatment selection or eligibility. Those differences can complicate attribution of observed outcomes to the intervention.
In this trial, surgical candidacy determined whether participants entered Arm A or Arm B. The primary outcome was restricted to Arm B, while Arm A followed a perioperative treatment schedule. These are not exchangeable control and treatment groups by design. Comparisons between their outcomes would be vulnerable to differences in clinical status and treatment pathway, and the registry explicitly notes that the arms are not a like-for-like control comparison.
What is over-dispersion, and is it relevant to this endpoint?
General statistical context. Over-dispersion occurs when observed variability in count data exceeds what a statistical model assumes. It can affect uncertainty estimates for certain count outcomes. It is not a generic adjustment that can be applied to every endpoint. Progression-free survival is a time-to-event outcome, so the specific question is how event times, censoring, and follow-up were handled, rather than whether a count model allowed for over-dispersion.
The registry record does not report the model used to estimate the median or its confidence interval. It also does not report a detailed statistical analysis plan. The appropriate method and its assumptions therefore cannot be evaluated from this record.
What do planning illustrations mean?
General statistical context. A sample-size calculation based on an assumed effect asks how much information a future study might need under specified statistical assumptions. A planning illustration is not an observed treatment effect and is not a measure of the probability that the completed trial detected an effect. It should not be described as observed power.
The record's planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with effects framed as fractions of an observed effect. For time-to-event outcomes, the stated planning approach concerns total events. These assumptions are described as a planning illustration, not the trial's own design. The trial's sample-size justification is not reported in the registry record, and no trial-specific planned sample size rationale can be inferred from those assumptions.
Overall, the statistical methods that can be identified are limited to the endpoint type, named summary measure, and confidence level. The analysis method, handling of censoring and missing observations, and inferential results are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several secondary outcome areas: intratumoral concentration, safety profile, and anti-tumor response. It also records four outcome measures. However, it does not report a multiplicity strategy, such as how inference across outcomes was prioritized or whether significance levels were adjusted. The statistical analysis plan is not reported in the registry record. Without that information, it is not possible to determine how multiple outcome assessments were intended to affect interpretation.
The record lists no analysis entries. The primary outcome estimate and its confidence interval are not reported, and no detailed secondary outcome estimates are included in the registry record. The number of participants included in each outcome analysis, the number with observed progression, and the extent of missing outcome data are not reported in the registry record.
General statistical context. Missing observations can reduce precision and may introduce bias if the likelihood of missingness is related to participants' outcomes or characteristics. Censoring is part of time-to-event analysis, but it is not interchangeable with every form of missing data. Interpreting a survival analysis generally requires knowing how follow-up ended, what event definitions were applied, and whether any participants were excluded from the analysis.
The registry does not describe the analysis population, exclusions, missing-data approach, or handling of participants who withdrew consent or stopped treatment. Arm B treatment could continue until progression, intolerability, or withdrawal of consent, but this treatment-stopping description does not reveal how those circumstances were handled in the outcome analysis. No assumptions about those procedures can be made from the 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 |
|---|---|---|---|
| Combined Arms | 6 | 11 | 54.5% |
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 |
|---|---|
| Combined Arms | 11 of 11 |
Most frequent serious adverse event terms
| Event term | Organ system | Combined Arms |
|---|---|---|
| cellulitis | Skin and subcutaneous tissue disorders | 1 of 11 |
| seizure | Nervous system disorders | 1 of 11 |
| fall | Injury, poisoning and procedural complications | 1 of 11 |
| lymphocyte count decreased | Investigations | 1 of 11 |
| lung infection | Infections and infestations | 1 of 11 |
| diarrhea | Gastrointestinal disorders | 1 of 11 |
| nausea | Gastrointestinal disorders | 1 of 11 |
| dizziness | Nervous system disorders | 1 of 11 |
| vomiting | Gastrointestinal disorders | 1 of 11 |
| headache | Nervous system disorders | 1 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Combined Arms |
|---|---|---|
| lymphocyte count decreased | Investigations | 8 of 11 |
| fatigue | General disorders | 6 of 11 |
| nausea | Gastrointestinal disorders | 5 of 11 |
| elevated alanine aminotransferase | Investigations | 5 of 11 |
| seizure | Nervous system disorders | 4 of 11 |
| hypophosphatemia | Metabolism and nutrition disorders | 4 of 11 |
| maculo-papular rash | Skin and subcutaneous tissue disorders | 4 of 11 |
| diarrhea | Gastrointestinal disorders | 3 of 11 |
| rash | Skin and subcutaneous tissue disorders | 3 of 11 |
| lung infection | Infections and infestations | 2 of 11 |
Serious events with the highest arm-level rate: cellulitis (9.1%), seizure (9.1%), fall (9.1%), lymphocyte count decreased (9.1%), lung infection (9.1%).
The registry reports adverse-event information for a combined-arms group. It lists 11 at risk for serious adverse events and 6 affected, and 11 at risk for other adverse events and 11 affected. The record also lists cellulitis, seizure, fall, lymphocyte count decreased, lung infection, and diarrhea among the top serious terms, each at 9.1%.
These figures should be read as registry-reported safety counts and terms, not as a comparison between bosutinib and a control treatment. The group combines the arms, which had different surgical eligibility and dosing pathways. The record does not provide arm-specific figures in the registry record, nor does it provide detail about timing, duration, severity grading, or attribution for each listed term. A listed adverse event does not by itself establish that bosutinib caused it.
The deaths field is null, so a death count is not reported in the registry record. The safety figures also do not describe the primary progression-free survival outcome. As with any adverse-event summary, the counts need the relevant analysis population and follow-up context for fuller interpretation; those details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this was a completed, open-label, non-randomized Phase 2 trial of bosutinib in adults with recurrent glioblastoma. It defines progression-free survival as the primary outcome for Arm B, measured from treatment initiation to progression, and identifies a median and 95% confidence interval as the planned summary. It also describes separate treatment pathways for participants who were and were not surgical candidates.
What the record does not establish is the numerical primary outcome. The median progression-free survival and its confidence interval are not reported in the registry record. No hazard ratio or analysis entries are listed. The record therefore cannot show the observed duration of progression-free survival, the precision of an estimate, or a statistical comparison with another treatment.
The adverse-event figures describe a combined-arms group, with serious and other events recorded separately and selected serious terms listed. They are not a controlled safety comparison, and the record does not provide enough detail to assess event attribution or differences between the arms. The figures should not be used as a substitute for the missing primary outcome results.
General statistical context. A trial's design, outcome definition, and results answer different questions. The design tells readers how participants entered the study and what was intended to be measured; an outcome estimate describes what was observed; uncertainty and design limitations inform how confidently that observation can be interpreted. In this case, the record allows the first question to be described, but does not report the principal numerical estimate needed for the second.
Accordingly, the record supports a careful account of the study's structure and the information it reports, but not a conclusion about the size or precision of the primary outcome or a causal treatment effect.
13. Why This Trial Matters Statistically
This trial illustrates why an endpoint definition and a numerical result are both necessary for statistical interpretation. The registry clearly identifies progression-free survival, its starting point, its event definition, and the population to which it applies. Yet the median and confidence interval are not reported in the registry record. A well-defined endpoint without its estimate cannot answer how the observed participants fared on that endpoint.
The non-randomized structure is also central. Arm A and Arm B were formed according to surgical candidacy and followed different dosing pathways. The primary outcome applies to Arm B only. These features limit direct comparisons across arms: a difference, if one were reported, could reflect differences in participant eligibility or care pathway as well as any difference associated with treatment. The registry itself cautions that the arms are not a like-for-like control comparison.
The record also separates treatment completion conditions from endpoint analysis. Arm B dosing continued until progression, intolerability, or withdrawal of consent, but the method for including participants who stopped treatment or lacked complete follow-up is not reported. This matters because outcome estimates depend on how event times and incomplete observation are handled.
General statistical context. Statistical reporting is most useful when it connects the design to the analysis population, the endpoint estimate, its uncertainty, and the assumptions behind the analysis. When one or more links are absent, readers should distinguish what the record documents from what would require additional evidence. That distinction is especially important in a study without random assignment or a control group.
The listed serious adverse-event figures provide some safety information, but their combined-arms presentation and missing contextual details prevent a controlled comparison. The trial therefore matters statistically as an example of the limits of interpreting registry records when design information is available but primary outcome estimates and analysis details are not.
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 principal limitation for interpreting efficacy is that the registry record does not report the primary progression-free survival median or its 95% confidence interval. It also does not report hazard ratios or analysis entries. The primary outcome therefore has a stated definition but no posted numerical estimate in the record.
The primary outcome applies only to Arm B, and the number of Arm B participants is not reported in the registry record. Overall enrollment was 36, but that total does not indicate how many participants contributed to the primary analysis. The record does not report progression event counts, follow-up duration by participant, or censoring information.
The non-randomized allocation and absence of masking limit interpretation. Participants entered different arms according to surgical candidacy, and the treatment schedules differed. Arm comparisons would not provide a like-for-like control comparison. The registry record does not report baseline characteristics or an adjustment strategy that could help describe or account for differences in the groups.
The timeframe field lists 2 years, while the primary outcome description specifies assessment at six months. The record does not explain the relationship between these time references. The statistical analysis plan, sample-size justification, interim analysis procedures, multiplicity strategy, missing-data methods, and analysis populations are not reported in the registry record.
Finally, safety information is reported for combined arms, without the detail needed to assess arm-specific patterns, event attribution, or full follow-up context. The deaths field is null. These limitations concern what can be interpreted from the registry record and do not establish that unreported analyses or information were absent from other sources.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Bosutinib in Adult Patients With Recurrent Glioblastoma — NCT01331291.
- Registry record last updated 2016-07-25; status last verified 2016-06.
- Results first posted 2016-06-20.
- 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
This completed, open-label Phase 2 trial evaluated oral bosutinib in adults with recurrent glioblastoma. The registry records non-randomized allocation, no masking, parallel arms, and enrollment of 36. Arm A enrolled surgical candidates; Arm B enrolled patients who were not surgical candidates.
The primary outcome was progression-free survival in Arm B, measured from treatment initiation to progression. The description refers to assessment at six months, while the timeframe field lists 2 years. The median and 95% confidence interval are not reported in the registry record, which also lists no analysis entries.
The registry lists intratumoral concentration, safety profile, and anti-tumor response as secondary outcomes. Its adverse-event information is for combined arms. The trial's sample-size justification, detailed statistical plan, and missing-data procedures are not reported in the registry record.