Study of Platelet Derived Growth Factor Receptor (PDGFR) in Recurrent Malignant Gliomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Platelet Derived Growth Factor Receptor (PDGFR) in Recurrent Malignant Gliomas (NCT01140568), a na phase 2 study. The primary outcome is Number of Patients Who Had 6-month Progression-free Survival..

2. Clinical Question

3. Trial Design

The registry identifies this as a Phase II study of a PDGFR kinase inhibitor in biomarker-enriched recurrent malignant gliomas. Its design is single-group, with allocation recorded as NA and masking recorded as none. The study is marked completed. It began on 2010-04-21, and primary completion is recorded as 2016-10-05.

The intervention was nilotinib. The arm description specifies a standard dose of 400mg taken by mouth twice a day until disease progression or development of unacceptable side effects. The stated study purpose was to assess survival, disease response, and side effects in patients with malignant gliomas positive for PDGFR amplification, and to test the hypothesis that this group is sensitive to PDGFR kinase inhibitors. That hypothesis is the study rationale, not a result.

The registry reports 38 enrolled patients and states that only 34 were treated. It does not explain the difference between enrollment and treatment, or say how people who enrolled but were not treated were handled in outcome analyses. The primary endpoint is a count of patients with six-month progression-free survival. Overall Response Rate is listed as a secondary outcome. A concurrent control group, random assignment, or masking procedure is not described. The registry record does not report a statistical analysis plan, sample-size justification, or details of interim analyses.

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.

Before assignment: 38 people were enrolled in the study and 34 were treated with study drug. When patients came off treatment they moved into survival follow up.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 38 patients were enrolled, but only 34 were treated

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 Number of Patients Who Had 6-month Progression-free Survival., measured over 6 months.

The primary endpoint is the number of patients who had progression-free survival at six months. It is a binary-outcome summary expressed as a participant count: each patient either meets the endpoint definition at the specified assessment or does not. The registry lists the unit as participants and identifies the outcome parameter as a count of participants.

Progression was defined using McDonald Criteria. The listed criteria include a 25% increase in the sum of products of all measurable lesions over the smallest sum observed, or over baseline if there was no decrease, using the same techniques as at baseline. Other criteria include clear worsening of evaluable disease, appearance of a new lesion or site, clear clinical worsening, or failure to return for evaluation due to death or deteriorating condition unless clearly unrelated to the cancer.

As a general statistical concept, a fixed-time progression-free endpoint can express how many participants remain free of progression by a specified assessment point. It is different from reporting the timing of each progression event or a time-to-event estimate across follow-up. The registry does not report the observed count, the corresponding proportion, or an uncertainty interval for this endpoint. It also does not explain why six months was selected as the assessment time.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count communicate?

The primary outcome is a count of participants meeting a defined endpoint, rather than a continuous measurement such as a laboratory value. For a binary outcome, participants are classified according to whether the endpoint is met. The count is easiest to interpret when its denominator and analysis population are clear. In this record, 38 patients were enrolled and 34 were treated, but the denominator used for the primary endpoint is not reported in the registry record. The actual endpoint count is also not reported, so no observed event proportion can be interpreted.

As a general statistical concept, a proportion estimates the frequency of an outcome in a defined group. Its uncertainty depends in part on the amount of information in that group and on how common the outcome is. A confidence interval expresses a range of values compatible with the observed data under the method used; it is not a guarantee that the true value lies in that range. No confidence interval for six-month progression-free survival is reported in the registry record.

Why does the endpoint definition matter?

An outcome is only interpretable if its criteria are sufficiently clear to understand which observations qualify. The registry describes progression by reference to McDonald Criteria and lists radiographic, clinical, and follow-up-related criteria. Those rules define what counts as progression for this endpoint; they do not, by themselves, state how assessments were scheduled, whether assessments were independently reviewed, or how disagreements were resolved. Those details are not reported in the registry record.

A fixed-time endpoint also depends on whether participants can be assessed at the specified time. The registry definition includes failure to return for evaluation due to death or deteriorating condition unless clearly unrelated to the cancer, but it does not describe the handling of other missing assessments, withdrawals, or incomplete follow-up. Missing outcome information can affect interpretation if the participants with unobserved outcomes differ from those assessed. The record does not report the extent of missing endpoint data or the method used to address it.

What can a single-group design estimate?

As a general statistical concept, a single-group study can describe outcomes observed among participants who received the intervention. It does not directly estimate a contrast with a concurrent control group. Without random assignment to treatment conditions, differences from outcomes in another population or historical experience may reflect differences in patient characteristics, study procedures, follow-up, or other factors as well as treatment. The registry identifies this trial as single-group and does not describe a comparator.

Randomization is commonly used in comparative trials to balance measured and unmeasured prognostic factors across treatment groups, on average. That general advantage does not apply as a between-group balancing mechanism in a single-group study. The trial design therefore places limits on causal interpretation even if a numerical outcome were available. The registry does not report an adjusted analysis that might address any measured prognostic factors.

What does the registry say about statistical testing?

The registry lists two outcome measures and zero analyses. It does not report a statistical analysis plan, test methods, estimates of uncertainty, or a sample-size justification. Statistical significance, model choice, covariate adjustment, and any planned handling of multiple outcomes are therefore not described in the registry record. Without the endpoint result and its analysis method, the precision and inferential strength of the primary outcome cannot be evaluated.

General statistical practice distinguishes an estimate from its uncertainty. An estimate describes the observed outcome in the study population, while an interval or other uncertainty measure conveys how much the data leave unresolved. A small p-value, if reported, would address compatibility with a specified null model, not the probability that the treatment is effective. Neither a p-value nor an uncertainty interval for the primary endpoint is reported, so those interpretations cannot be applied to this record.

How should planning illustrations be read?

Sample-size calculations are planning illustrations, not observed power. The stated assumptions for planning illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. Those assumptions describe a hypothetical planning framework and do not describe the actual single-group allocation in this trial. They should not be read as the trial's own design justification or as evidence that the trial had a particular probability of detecting an effect. The registry record does not report the trial's sample-size justification.

As a general concept, power calculations depend on assumptions about the outcome, the effect to detect, the variability or event frequency, the testing procedure, and the planned allocation. A planning result is conditional on those assumptions. It does not show what the study actually found, and it cannot substitute for an observed estimate with its uncertainty. The posted registry information does not include numerical planning results that can be interpreted alongside the primary endpoint.

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("Nilotinib")
n      <- c(34)
events <- c(3)
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  Nilotinib  34  3  8.8  1.9  23.7  3.0  23.0  3.2  23.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary six-month progression-free survival count and Overall Response Rate as a secondary outcome. It does not report an analysis plan describing which outcomes were tested, how statistical tests were ordered, or whether any adjustment for multiple comparisons was intended. The number of outcomes alone does not establish that a multiplicity adjustment was or was not necessary; the inferential plan is not reported in the registry record.

The registry lists zero analyses. It does not provide a numerical primary endpoint result or a result for the secondary outcome in the record. Consequently, no estimates, confidence intervals, p-values, or adjusted analyses are available for interpretation. The absence of a listed analysis is not evidence that an analysis was performed and found no effect.

Missing-data handling is also not reported in the registry record. Although 38 patients were enrolled and only 34 were treated, the record does not explain the status or outcomes of those not treated. It does not specify the population used for the primary endpoint, the number with an assessable six-month outcome, or how missed evaluations and incomplete follow-up were addressed. The endpoint definition includes a particular rule concerning failure to return because of death or deteriorating condition unless clearly unrelated to the cancer, but this does not describe handling of every possible missing observation.

As a general statistical concept, multiplicity can increase the chance of a false-positive finding when several hypotheses are tested, while missing data can affect estimates if the observed participants are not representative of those whose outcomes are unavailable. Those issues cannot be resolved from the available registry entries.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: musculoskeletal tissue disorder-other: muscle spasm (2.9%), generalized muscle weakness (2.9%), hydrocephalus (2.9%).

The safety entry is for the nilotinib group and records 34 participants at risk. It reports 3 participants affected by serious adverse events, 24 affected by other adverse events, and 0 deaths. These are descriptive counts from the registry record; they do not by themselves indicate whether an event was caused by the study drug, nor do they provide a comparison with another treatment group.

The listed serious-event terms are “Musculoskeletal tissue disorder-other: Muscle Spasm,” “Generalized Muscle Weakness,” and “Hydrocephalus,” each reported as 2.9%. The registry also reports the serious-event group count separately. The listed percentages should be read as the values recorded for those terms, not as comparative risk estimates. The record does not provide event narratives, timing, severity beyond the serious classification, or an attribution assessment for each term.

As a general statistical concept, safety counts depend on how events are defined, collected, and classified, and on the participants included in the risk denominator. A single-group safety summary describes recorded events among participants in that group. Without a comparator, it cannot show whether the frequency is higher or lower than it would have been under another condition. The registry does not report additional detail about follow-up duration for safety events.

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

The registry establishes that a Phase II, single-group study evaluated nilotinib in recurrent malignant gliomas positive for PDGFR amplification, with six-month progression-free survival as the primary endpoint. It also documents the endpoint definition, lists Overall Response Rate as a secondary outcome, and reports selected safety counts. These registry entries describe the question and design; they do not provide a numerical answer to the primary efficacy question.

The six-month progression-free survival count is not reported in the registry record. Without it, no observed response frequency, estimate of precision, or test of statistical evidence can be discussed. The registry also lists no analyses, so there is no reported inferential result to interpret. This absence does not mean the study observed no progression-free participants, no responses, or no treatment effect; it means those results are not reported in this record.

Even a reported outcome from this design would need to be interpreted as an observation in a single treated group. Without a concurrent control group or randomized comparison, an observed outcome could not establish how outcomes would differ under another treatment or no study intervention. The design is not a like-for-like comparison, and the registry does not describe a causal comparative analysis.

The safety counts show that the registry recorded serious and other adverse events among participants at risk, and the serious-event entry includes 0 deaths. These figures do not establish that nilotinib caused or did not cause any event. They are not comparative estimates, and the record does not provide detailed event-level context.

The most defensible reading is therefore limited: the registry describes a completed study, its intervention, its intended primary endpoint, its enrollment and treatment counts, and selected safety information, while leaving the numerical primary outcome and statistical analyses unreported. No claim that the treatment works or does not work follows from the information recorded.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a biologically selected population and a comparative design. The registry describes recurrent malignant gliomas positive for PDGFR amplification, reflecting a biomarker-enriched research question. Selecting participants by a biomarker defines the population to which an outcome would apply, but it does not by itself establish that the biomarker predicts treatment benefit. A comparative analysis would be needed to evaluate whether outcomes differ by treatment in a way linked to biomarker status; no such comparison is described in this single-group record.

The primary endpoint is a count at a fixed assessment time, while the study purpose also refers to survival and disease response. These are related clinical concepts, but they are not interchangeable statistical outcomes. A participant count at six months does not communicate the full timing of progression events, and a response-rate outcome does not substitute for progression-free survival. The registry lists Overall Response Rate as secondary but does not report its numerical result.

The difference between enrolled and treated populations also matters. The record states that 38 patients were enrolled and 34 were treated, yet it does not report the endpoint denominator or explain how those not treated were handled. Transparent accounting of populations is essential for understanding what an outcome estimate describes and how missing information may affect it.

Finally, statistical importance depends on reported estimates and their uncertainty, not only on the study's phase or biological rationale. Because the registry lists no analyses and does not report the primary result, readers cannot assess the size or precision of an outcome. This makes clear reporting of endpoint results and analysis populations especially important for interpreting this trial.

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 central limitation for statistical interpretation is that the numerical primary endpoint result is not reported in the registry record. The outcome is named and defined, but there is no reported count of participants with six-month progression-free survival, denominator, estimate, or uncertainty interval. The listed secondary outcome, Overall Response Rate, also has no reported numerical result in the record.

The trial is single-group, with allocation recorded as NA and masking as none. No concurrent control group is described, so the design does not support a direct randomized comparison. An observed outcome, if reported, would describe the study group but would not on its own isolate a treatment effect from other influences.

The registry reports 38 patients enrolled and only 34 treated. It does not explain why some enrolled patients were not treated, identify the analysis population, or state how the primary endpoint denominator was determined. It also does not report how missed assessments, withdrawals, or other incomplete follow-up were handled. The endpoint definition specifies one circumstance involving failure to return for evaluation, but does not provide a comprehensive missing-data plan.

Further trial details that could affect interpretation are not reported in the registry record, including a statistical analysis plan, sample-size justification, interim-analysis approach, and methods for addressing multiplicity. The registry's safety information is limited to group counts and selected serious-event terms; detailed event-level context and attribution are not reported. These limitations constrain both efficacy interpretation and assessment of the precision and context of the safety findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Platelet Derived Growth Factor Receptor (PDGFR) in Recurrent Malignant Gliomas — NCT01140568.
• Registry record last updated 2020-05-05; status last verified 2020-04.
• Results first posted 2020-04-24.
• 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 identifies NCT01140568 as a completed Phase II, single-group study of nilotinib in recurrent malignant gliomas positive for PDGFR amplification. The record reports 38 enrolled patients and 34 treated patients. The planned regimen was 400mg by mouth twice a day until progression or unacceptable side effects.

The primary endpoint was the number of patients with six-month progression-free survival, defined using McDonald Criteria. Overall Response Rate is listed as a secondary outcome. The numerical primary result, secondary outcome result, and statistical analyses are not reported in the registry record.

The safety entry records 34 participants at risk, 3 with serious adverse events, 24 with other adverse events, and 0 deaths. Three serious-event terms are listed at 2.9% each. The single-group design and absence of reported efficacy analyses limit conclusions about comparative treatment effects.