Dovitinib in Treating Patients With Recurrent or Progressive Glioblastoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dovitinib in Treating Patients With Recurrent or Progressive Glioblastoma (NCT01753713), a non-randomized phase 2 study. The primary outcome is Arm 1: Progression Free Survival (PFS).

2. Clinical Question

3. Trial Design

This is a phase II study of dovitinib in patients with recurrent or progressive glioblastoma. The registry record lists a parallel model, non-randomized allocation, and no masking. Enrollment is recorded as 33, and the study status is completed. The record lists a start date of 2012-12-20 and a primary completion date of 2015-01-28.

The study separated patients according to prior anti-angiogenic therapy. The anti-angiogenic therapy-naive group comprised patients who had progressed without such therapy. The other group comprised patients who had progressed on anti-angiogenic therapy. Both groups received dovitinib orally 5 days a week, with courses repeating every 4 weeks unless disease progression or unacceptable toxicity occurred. This design describes treatment in each group, not a randomized comparison of dovitinib with another treatment.

The group definitions are clinically relevant to interpreting results: prior therapy status distinguishes the populations, and may also be associated with differences between them. Because allocation was non-randomized, any difference in outcomes between the groups cannot be attributed to prior therapy status or dovitinib alone from this record. The registry record does not report how patients entered each group, whether other baseline characteristics were balanced, or whether any adjustment was planned to account for group differences.

The primary outcome is described for the anti-angiogenic therapy-naive group and concerns progression-free survival at 6 months. Secondary outcomes listed are toxicity assessed using CTCAE Version 4.0, objective response rate using modified revised RANO criteria, median progression-free survival, and overall survival. The record lists 7 outcome measures, but does not report their individual results in the registry record for this analysis. The statistical analysis plan, sample-size justification, and details of analysis populations are not reported in the registry record.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Arm 1: Progression Free Survival (PFS), measured over 6 months.

The primary endpoint is the number of anti-angiogenic therapy-naive patients with recurrent glioblastoma who were progression-free at 6 months. The registry record defines progression-free survival as the time from randomization to objective tumor progression or death. It defines PFS-6 as having complete response, partial response, or stable disease at 6 months, assessed using RANO criteria. The listed descriptions define complete response as total disappearance of lesions, partial response as >50% reduction in lesions, and stable disease as <25% reduction in lesions.

A six-month progression-free endpoint is one way to describe whether patients remain alive without documented progression at a specified follow-up point. In general, a time-to-event endpoint incorporates both the occurrence and timing of progression or death; a fixed-time summary focuses on status at the stated time. The chosen endpoint can therefore offer a clinically interpretable snapshot, while a fuller time-to-event analysis can convey information across follow-up. The registry record lists median progression-free survival separately as a secondary outcome.

The endpoint description uses the phrase “time from randomization,” although the study is recorded as non-randomized. That wording leaves the time origin unclear in this record; an alternative origin is not reported in the registry record. The primary endpoint’s observed count or proportion and any uncertainty interval are also not reported in the registry record. The endpoint definition alone therefore does not establish how many patients met it or how precise any estimate may be.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish what this record describes from what it can establish. The endpoint is a fixed-time progression-free survival summary within one group, whereas the study has two non-randomized groups and several listed secondary outcomes. The record does not report the primary endpoint value, an uncertainty interval, a hypothesis test, or a detailed statistical analysis plan. The following concepts are general explanations, not descriptions of unreported procedures used in this trial.

What does a fixed-time progression-free endpoint represent?

In general, progression-free survival measures the time until a defined event, commonly disease progression or death. A fixed-time endpoint asks whether a participant has remained free of those events through a specified follow-up time. Here, the registry identifies 6 months and defines PFS-6 using response categories at that time. This produces a readily interpretable status summary, but its meaning depends on clear event definitions, consistent assessment, and appropriate handling of participants whose status is unknown at the time point.

The record’s wording also refers to time from randomization, despite recording non-randomized allocation. A time origin is needed to define follow-up consistently. The record does not clarify that wording or report an alternative origin. It also does not say how assessments were scheduled, how progression dates were established, or how deaths without documented progression were handled in the analysis beyond including death in the stated endpoint definition.

Why do time-to-event analyses need follow-up information?

In general, time-to-event methods can use information from participants with different lengths of follow-up. Participants who have not experienced the event by their last known assessment may be censored, meaning that their later event status is unknown rather than assumed to be event-free indefinitely. The validity of such methods depends on appropriate censoring assumptions and accurate follow-up information. The registry record lists median progression-free survival as a secondary outcome, but does not report the estimate, the number of events, censoring details, or the method used to calculate it.

A fixed-time status can be less informative if follow-up to the stated time is incomplete or differs across participants. In general, missing status at the time point requires a prespecified approach; excluding participants, treating them as events, or using other methods can lead to different summaries. The analysis population, completeness of follow-up, and missing-data approach are not reported in the registry record. No single handling method should be inferred.

What does non-randomized allocation imply?

Random assignment, in general, helps create groups that are comparable on measured and unmeasured factors at the start of a study. This study is recorded as non-randomized and its groups are defined by prior anti-angiogenic therapy. The groups therefore represent different treatment histories, not randomly assigned alternatives. Their outcomes may differ for reasons other than the study treatment. A simple contrast between groups would be descriptive unless supported by appropriate design and analysis; adjusted estimates and adjustment methods are not reported in the registry record.

The record says the study uses a parallel model, which means that the groups are described as separate treatment groups rather than as a crossover sequence. Both groups are listed as receiving dovitinib. The record does not identify a placebo or active-control group. Thus, the design as described does not provide a randomized estimate of dovitinib versus another treatment.

How should uncertainty and statistical significance be read?

In general, a confidence interval describes a range of values compatible with the data under a specified statistical model and conveys estimation uncertainty. A narrow interval indicates greater precision than a wide interval, but neither width nor a p-value establishes that a finding is clinically important. A p-value is a measure of how unusual the observed data would be under a specified null model; it is not the probability that a treatment works. The registry record does not report a primary estimate, confidence interval, p-value, or test for the endpoint.

With sparse outcome information, the direction and precision of an effect cannot be inferred from the treatment schedule or from adverse-event counts. A result should be interpreted alongside its denominator, follow-up, uncertainty, and analysis population. Those details for the primary endpoint are not reported in the registry record.

Why does multiplicity matter?

In general, evaluating several outcomes or several statistical tests can increase the chance of at least one apparently notable result by chance. Multiplicity can be addressed through a prespecified hierarchy, adjusted testing, or careful emphasis on estimation and the primary endpoint. The record lists several secondary outcomes and 7 outcome measures, but does not report a multiplicity strategy or the number of tests actually conducted. It lists no analyses in the registry record for this explanation. That absence does not establish that no analyses occurred; analysis details are not reported in the registry record.

What are the planning illustrations?

In general, a sample-size calculation describes how many participants a hypothetical study might need under stated assumptions about effect size, allocation, significance level, and statistical method. The stated planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a fraction of the observed effect. For time-to-event calculations, the illustrations concern total events; other calculations concern participants per arm.

These are planning illustrations based on an observed effect, not the trial’s own design justification. They are not observed power and do not show that the trial had a particular probability of detecting an effect. The registry record does not report its sample-size justification or the numerical estimates needed to evaluate the planning illustrations in detail.

Why can event counts be hard to compare?

In general, adverse-event counts depend on the definition of an event, the observation period, exposure, and whether counts refer to participants or event episodes. Over-dispersion is a general feature of count data in which variability exceeds what a simple model assumes; it can make standard errors too small if the model does not account for it. The registry identifies the adverse-event measure as participants with an event, but does not provide modeling details or event-level data. The posted counts should therefore be read as descriptive participant counts, not as a modeled comparison.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Anti-angiogenic Therapy Naive Patients", "Anti-angiogenic Therapy Patients")
n      <- c(19, 14)
events <- c(0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Anti-angiogenic Therapy Naive Patients  19  0  0.0  0.0  17.6  0.0  16.8  0.1  16.8
ARM  Anti-angiogenic Therapy Patients  14  0  0.0  0.0  23.2  0.0  21.5  0.2  21.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and several secondary outcomes: toxicity assessed using CTCAE Version 4.0, objective response rate using modified revised RANO criteria, median progression-free survival, and overall survival. It also reports 7 outcome measures. Considering multiple outcomes can complicate interpretation because, in general, repeated testing can make chance findings more likely. A prespecified testing hierarchy or multiplicity adjustment can help control that issue. Such a strategy is not reported in the registry record.

The record lists no analyses in the registry record for this explanation. This does not show that investigators performed no analyses; it means that the analysis details are not reported in the registry record. The statistical plan, including whether outcomes were tested, which tests were used, and whether any interim analyses were planned or conducted, is not reported in the registry record.

Missing-data handling is also not reported in the registry record. The available description does not specify how patients without an assessment at 6 months were treated, whether follow-up differed between groups, or how incomplete time-to-event follow-up was handled. These choices matter because an unknown outcome is not automatically equivalent to progression, death, or continued progression-free status.

The record does not report the analysis population for the primary endpoint or secondary outcomes, nor whether analyses included all enrolled patients or a defined subset. It does not describe exclusions, withdrawals, or reasons for missing assessments. Without these details, the endpoint’s denominator and potential selection effects cannot be evaluated. The primary endpoint result itself is not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thromboembolic event (31.6%), confusion (15.8%), death nos (14.3%), seizure (10.5%), acute kidney injury (10.5%).

The registry adverse-event fields list serious adverse events for the anti-angiogenic therapy-naive group as 10 participants affected among 19 at risk, and for the anti-angiogenic therapy group as 7 participants affected among 14 at risk. The corresponding fields for other adverse events list 19 participants affected among 19 at risk and 14 among 14. These are participant counts, not counts of separate event episodes. The record also lists deaths as 1 in the naive group and 2 in the therapy group.

Selected serious-event terms are listed with percentages: thromboembolic event, 31.6%; confusion, 15.8%; death NOS, 14.3%; seizure, 10.5%; acute kidney injury, 10.5%; and colitis, 7.1%. The denominator used for these term-specific percentages is not reported in the registry record. The figures should not be added together: a participant may have more than one event, and the record does not state whether categories overlap.

These data describe events recorded in the groups. They do not by themselves show that dovitinib caused an event, and the listed deaths should not be interpreted as treatment-related without attribution information. Event severity definitions beyond the serious-event label, exposure duration, and causal assessments are not reported in the registry record.

13. What the Result Does, and Does Not, Mean

The record establishes that a phase II study of dovitinib was completed in patients with recurrent or progressive glioblastoma and that patients were grouped by prior anti-angiogenic therapy. It describes the dosing schedule and identifies progression-free survival at 6 months in the therapy-naive group as the primary endpoint. It also lists secondary outcomes and reports adverse-event counts and selected serious-event percentages.

Those details do not establish the primary endpoint result. The number of patients meeting PFS-6, an effect estimate, and an uncertainty interval are not reported in the registry record. The secondary outcome results are also not reported in the registry record for this analysis. As a result, the record does not allow a quantitative judgment of the study’s efficacy findings or their precision.

The study’s two groups are not randomized treatment alternatives. Both are described as receiving dovitinib, and group membership reflects prior anti-angiogenic therapy history. Any difference between group outcomes could be related to that history or to other differences between the groups. Without randomization, reported baseline information, and an appropriate comparative analysis, a group contrast would not establish a causal effect.

The adverse-event figures can describe the recorded frequency of participants with events in each group, but they do not prove that the treatment caused those events. The record does not give the attribution details or denominator basis for the selected serious-event percentages. Nor do the registry entries describe exposure time, missing safety data, or the analysis population.

In general, a study’s result is most informative when an outcome estimate is considered alongside its uncertainty, the people included in the analysis, follow-up completeness, and design limitations. Here, the primary estimate and several of those supporting details are not reported in the registry record. The study description and posted safety counts therefore characterize what was planned and recorded, but do not support a conclusion about treatment efficacy or comparative benefit.

14. Why This Trial Matters Statistically

This trial illustrates why design details matter when interpreting clinical outcomes. The registry identifies a phase II study with non-randomized allocation, a parallel model, no masking, and two groups distinguished by prior anti-angiogenic therapy. Although both groups are described as receiving dovitinib, their different histories mean they cannot be treated as equivalent arms of a randomized comparison. Statistical interpretation must begin with that design context rather than treating any group difference as a treatment effect.

The primary endpoint also shows the importance of an explicit outcome definition. The record specifies progression-free survival at 6 months and describes response categories used to define PFS-6. Yet its wording refers to time from randomization despite the non-randomized design. That mismatch makes the stated time origin unclear and highlights why endpoint definitions should be aligned with the study design.

Outcome reporting is as important as outcome selection. The record names a primary endpoint and secondary outcomes, but the primary result and the secondary results are not reported in the registry record for this analysis. Without estimates and their uncertainty, readers cannot assess precision or distinguish an imprecise result from a more informative one. A completed status does not itself supply an outcome finding.

The safety information offers another statistical lesson: participant counts, event terms, and percentages answer different questions. Counts can describe how many participants had recorded events, while term-specific percentages require a clear denominator and may overlap. The record does not report the denominator basis for the selected serious-event percentages or causal attribution for the listed deaths. Clear definitions and denominators are necessary for meaningful interpretation.

Finally, planning illustrations based on an observed effect are not evidence that a completed trial had adequate power, and they are not observed power. This distinction is important whenever planning calculations accompany results. The registry record does not report the trial’s own sample-size justification. Together, these issues underscore the need to evaluate design, endpoint definition, analysis, uncertainty, and reporting as separate parts of the evidence.

15. 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 primary endpoint result is not reported in the registry record. The endpoint description identifies the population and the 6-month assessment but does not provide the observed count, estimate, or uncertainty. Secondary outcomes are listed without results in the registry record for this analysis, so they cannot fill that gap.

The non-randomized design limits causal interpretation. Patients were grouped according to whether they had progressed without or on anti-angiogenic therapy, so these groups differ by treatment history. The registry record does not report baseline characteristics, allocation procedures, or adjusted analyses that might help describe or account for group differences. It also does not identify a randomized control group.

The primary endpoint wording refers to time from randomization even though allocation is recorded as non-randomized. The record does not clarify the time origin. It also does not report assessment timing, endpoint adjudication procedures, censoring rules, or how progression and death were handled in the analysis beyond the general definition.

Analysis populations and missing-data methods are not reported in the registry record. The available information does not establish how many patients had an assessable 6-month outcome or how incomplete follow-up was handled. The sample-size justification, statistical analysis plan, multiplicity strategy, and any interim analyses are also not reported in the registry record.

Safety interpretation has further constraints. The record lists participant counts with serious and other adverse events, deaths, and selected serious-event percentages, but does not provide the denominator basis for those term percentages, causal attribution, exposure duration, or detailed event-level data. These omissions prevent a fuller assessment of event patterns and comparability between the groups.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dovitinib in Treating Patients With Recurrent or Progressive Glioblastoma — NCT01753713.
• Registry record last updated 2017-12-12; status last verified 2017-10.
• Results first posted 2017-08-08.
• 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.

19. Record Summary

The registry record describes NCT01753713, a completed phase II study of dovitinib in patients with recurrent or progressive glioblastoma. It records enrollment of 33, non-randomized allocation, a parallel model, and no masking. The start date is 2012-12-20, and the primary completion date is 2015-01-28.

Patients were grouped by whether they had progressed without or on anti-angiogenic therapy. Both groups were scheduled to take dovitinib orally 5 days a week, with courses repeating every 4 weeks unless progression or unacceptable toxicity occurred. The primary endpoint is described as the number of therapy-naive patients progression-free at 6 months.

Secondary outcomes include toxicity, objective response rate, median progression-free survival, and overall survival. The record also lists serious and other adverse-event counts, deaths, and selected serious-event terms. The primary endpoint result, secondary outcome results, statistical analysis plan, sample-size justification, and missing-data methods are not reported in the registry record.