Everolimus for Children With Recurrent or Progressive Ependymoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Everolimus for Children With Recurrent or Progressive Ependymoma (NCT02155920), a na phase 2 study. The primary outcome is Objective Response Rate (Complete Response Rate and Partial Response Rate) Following Treatment With Everolimus for Children With Recurrent or Progressive Ependymomas..

2. Clinical Question

The question is therefore whether participants in this treated group had a complete or partial response under the registry’s stated definitions. It is not a randomized comparison of everolimus with another treatment or with no treatment. Without a concurrent control group, the study design cannot separate outcomes associated with treatment from other possible influences on the course of disease.

The registry summary describes the rationale as prior laboratory and clinical observations related to the mTOR pathway. Those observations are background rationale, not results of this study. The record does not report the number of participants who had a complete response, a partial response, or no response. The observed response rate for this trial is therefore not reported in the registry record.

3. Trial Design

This was a phase II, single-group study of everolimus in children with recurrent or progressive ependymoma. The registry lists allocation as NA and masking as none. Enrollment was 11, and the study status is completed. The study start is recorded as 2015-02, with primary completion on 2023-07-14.

The intervention was everolimus. The recommended dose is recorded as 4.5 mg/m2/dose once daily, with treatment planned for up to 2 years or until disease progression or unacceptable toxicity. The primary outcome timeframe is 2 years. These descriptions define the treatment and assessment plan in the registry; they do not establish how long any individual participant actually received treatment or completed follow-up.

Because the design has one group, the observed outcomes would describe participants who received the intervention, but would not provide a randomized estimate of how outcomes compare with an alternative. No control arm or allocation process is described. The record does not report the protocol’s sample-size justification, eligibility details beyond the population description, or further information about outcome assessment procedures.

The registry lists duration of response, progression-free survival, event-free survival, adverse events, and upregulated biomarkers of mTOR activation among secondary outcomes. It does not report analysis results for these outcomes in the registry record for this account. The number of listed analyses is 0. Completion status and the primary completion date do not by themselves indicate that an endpoint result was posted.

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: Eleven patients met the eligibility criteria and were enrolled on the study.

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 Objective Response Rate (Complete Response Rate and Partial Response Rate) Following Treatment With Everolimus for Children With Recurrent or Progressive Ependymomas., measured over 2 years.

The primary endpoint is the objective response rate, described as the complete response rate and partial response rate following everolimus treatment. The timeframe is 2 years, and the endpoint unit is participants. A complete response is defined as disappearance of all enhancing measurable and non-measurable disease. A partial response is defined as at least a 50% decrease from baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions.

General: An objective response endpoint classifies participants using prespecified changes in disease measurements. It is used to describe tumor response without relying only on a participant’s or investigator’s overall impression. Combining complete and partial responses into a response-rate measure can provide a compact summary of how many participants met either response definition. The meaning of that summary depends on the assessment rules, timing, and completeness of follow-up.

The registry record does not report the number of complete responses, partial responses, or participants assessed for the endpoint. It also does not report a calculated response rate or a confidence interval. Accordingly, the endpoint’s definition is available, but the trial’s observed primary endpoint result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The information available describes the design and endpoint, but not a complete statistical analysis plan or primary outcome analysis. The study is identified as phase II and single-group, with 11 participants enrolled. The primary endpoint is a participant-based count of complete and partial responses over a 2-year timeframe. No primary endpoint result, confidence interval, or test result is reported in the registry record.

What does a single-group design estimate?

General: A single-group study records outcomes in participants who receive the intervention. Its direct statistical summary is the observed outcome in that group, such as a count or proportion meeting an endpoint definition. Without a concurrent comparison group, it does not directly estimate a treatment-versus-control contrast. Differences in patient characteristics, disease course, follow-up, or other care cannot be accounted for by random allocation to treatment groups when there is only one group.

For this trial, the record does not provide the response count or the number assessed. It is therefore not possible to state the observed response proportion or assess its precision. The stated enrollment of 11 is a study-level enrollment figure, not a substitute for a reported endpoint denominator.

How should a response endpoint be read?

General: A response endpoint applies prespecified categories to observed measurements. Here, complete response refers to disappearance of all enhancing measurable and non-measurable disease. Partial response refers to at least a 50% decrease in the sum of products of perpendicular diameters of measurable enhancing lesions compared with baseline. The operational definitions make the endpoint more explicit, but interpreting a result would also require knowing how many participants were evaluated, how missing assessments were handled, and what assessment schedule and review procedures were used. Those details are not reported in the registry record.

The endpoint is framed as an objective response rate, but the record does not provide the numerator, denominator, or a confidence interval. General: a confidence interval conveys uncertainty around an estimate under a statistical model and method. For a participant-based response measure, the estimate’s precision depends in part on the amount of observed data. No interval can be discussed for this trial’s response endpoint because no estimate is reported.

What do the analysis listings tell us?

The record lists 0 analyses. This means that no statistical analysis result is included in the analysis information summarized for this account. It does not establish whether analyses were conducted outside the registry entry. The statistical test for the primary outcome, any adjustment or stratification, and any method for deriving uncertainty are not reported in the registry record.

The record also does not report a sample-size justification. General: a sample-size calculation is a planning exercise based on assumptions about a target effect, variability or event frequency, significance level, power, and design. It is distinct from an analysis of observed trial outcomes. The planning illustration associated with the study uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a stated fraction of the observed effect. Those are illustration assumptions, not a description of this trial’s single-group design or its enrollment rationale. No calculated planning values or observed primary effect are reported in the registry record. Any such sample sizes are planning illustrations, not observed power.

General: over-dispersion matters when observed variability exceeds what a model assumes. If a model assumes less variability than the data contain, uncertainty may be understated and inferential results may be misleading. The primary outcome is described as participant counts, and no model or dispersion estimate is reported, so no conclusion about over-dispersion in this trial can be made.

The registry lists secondary outcomes but does not give their estimates or analysis methods. The record does not report whether analyses were interim or final beyond the study status and completion information, nor does it report a prespecified hierarchy or other statistical plan. Statistical details beyond the endpoint definition and design description are not reported in the registry record.

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("Everolimus")
n      <- c(11)
events <- c(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  Everolimus  11  0  0.0  0.0  28.5  -0.0  25.9  0.2  26.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcome areas: the primary objective response endpoint and secondary outcomes covering duration of response, progression-free survival, event-free survival, adverse events, and upregulated biomarkers of mTOR activation. Considering multiple outcomes can raise a multiplicity issue. General: when several hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan specifies how results will be interpreted or adjusted. The registry record does not report a multiplicity strategy, endpoint hierarchy, or adjustment for multiple testing.

The record does not report how missing primary endpoint assessments were handled, whether any participants were excluded from an analysis, or which analysis population was used. It does not give the number of participants assessed for response or describe whether all enrolled participants were included in the primary analysis. These omissions matter because the interpretation of a response count depends on the analysis denominator and on how unavailable assessments are treated.

The sample-size justification is not reported in the registry record. Interim analyses and stopping rules are also not reported. Although the study status is completed, that status alone does not explain the statistical procedures used or establish which analyses were performed. The record lists 0 analyses, so no endpoint analysis results or analysis populations are available in the registry information.

General: missing-data methods and multiplicity procedures should be interpreted in light of the prespecified analysis plan. Without those details, readers cannot determine whether the reported results, if available elsewhere, reflect a particular imputation, exclusion, or testing strategy. For this study, the primary endpoint result and these analysis details are 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

Serious events with the highest arm-level rate: pneumonia (9.1%).

The registry records adverse-event information for 11 participants. One participant is listed as having a serious adverse event, and 0 participants are listed as having other adverse events in the corresponding counts. Pneumonia is the listed top serious adverse-event term, at 9.1%. The record also reports 10 deaths.

These counts require careful interpretation. The registry record does not report the timing, cause, or treatment relationship of the deaths. It does not state whether the serious adverse event was considered related to everolimus, nor does the available information give event-level detail or severity grades. The pneumonia entry is a reported term; it should not be taken as a complete account of all serious events or as evidence about causation.

General: adverse-event counts describe recorded events under the study’s reporting definitions. They do not, on their own, establish that an intervention caused an event or provide a direct comparison of safety between treatments. The study has no control group described, and a single-group count cannot provide a randomized comparative safety estimate. The registry record does not report further details needed to interpret the deaths or attribute individual events.

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

The record establishes that a completed phase II study enrolled 11 children with recurrent or progressive ependymoma and evaluated everolimus in a single-group design. It defines the primary objective response endpoint and gives the treatment schedule and intended timeframe. It does not report the primary response count, response rate, or uncertainty interval. Consequently, the posted registry information does not establish how many participants met the complete or partial response definitions.

The record’s rationale cites earlier laboratory findings and clinical observations involving the mTOR pathway and sirolimus. Those statements explain why the study was undertaken; they are not evidence of the outcome of this everolimus study. The study-specific response outcome cannot be inferred from that background rationale.

The single-group design also limits what any outcome could establish. General: a treated-group outcome can describe what occurred among participants in that group, but a randomized comparator is needed to estimate a treatment contrast protected by random assignment. This study is not described as having a comparator group, so it cannot provide a randomized estimate of the difference between everolimus and another treatment.

The reported safety counts provide limited descriptive information. The record lists one participant with a serious adverse event, 0 with other adverse events, pneumonia at 9.1% among the top serious terms, and 10 deaths. It does not report the causes or timing of deaths or the relationship of events to treatment. These counts do not support conclusions about comparative safety or causation.

The study’s completed status and dates document its registry status and timeline, not the size, precision, or interpretation of its clinical outcomes. The primary result, the statistical analysis details, and the handling of missing data are not reported in the registry record. Conclusions about response or comparative effects therefore cannot be drawn from the posted information.

14. Why This Trial Matters Statistically

This study is statistically important as an example of how a phase II single-group design frames an early clinical question. Its primary endpoint is specified in participant-level terms, with definitions for complete and partial response and a 2-year timeframe. Such definitions make clear what outcome the study intended to assess, even when the registry record does not include the observed result.

The distinction between rationale and trial evidence is especially relevant. The registry summary describes prior biological and clinical observations that motivated investigation of everolimus. Those observations provide context for the research question, but they do not replace an outcome analysis in the current participants. A statistically sound reading keeps the background rationale separate from the study’s own evidence.

The design also illustrates the limits of interpreting a single group. A response count, if reported, would describe outcomes in enrolled participants; it would not be a randomized comparison with another treatment. Design determines which statistical claims are supportable, irrespective of how compelling a biological rationale may be.

Finally, an endpoint definition is not the same as an endpoint result. The record provides the response criteria and enrollment information, but not the count of responses, the analysis denominator, or a measure of uncertainty. Without those elements, the primary response estimate and its precision cannot be assessed. The registry also lists secondary outcome areas without their results or analysis methods. These omissions make transparent reporting of estimates, denominators, and analytic decisions central to any complete statistical interpretation.

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 main trial-specific limitation in the registry information is the absence of the primary endpoint result. Although the objective response endpoint is defined, the record does not report complete responses, partial responses, the number assessed, a response rate, or a confidence interval. Enrollment of 11 does not show how many participants contributed evaluable response data.

The study is single-group and has no comparator arm described. As a result, the design does not yield a randomized comparison with another intervention. The record also does not report participant-level characteristics, follow-up completeness, the timing or frequency of response assessments, or procedures for review of measurements. These details would help readers understand how the endpoint was ascertained.

The registry does not report the statistical analysis plan, sample-size justification, analysis populations, missing-data methods, multiplicity handling, or interim analyses. It lists 0 analyses. Secondary outcomes are named, but their estimates are not included in the information.

Safety information is also limited. The record gives counts and a serious-event term, but not the timing or cause of the 10 deaths, the relationship of events to treatment, or further event-level detail. These limitations restrict interpretation of both efficacy and safety; they do not determine what analyses may exist outside the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Everolimus for Children With Recurrent or Progressive Ependymoma — NCT02155920.
• Registry record last updated 2024-05-08; status last verified 2024-04.
• Results first posted 2024-05-08.
• 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 a completed phase II, single-group study of everolimus in children with recurrent or progressive ependymoma. Enrollment was 11. The study start is recorded as 2015-02, and primary completion as 2023-07-14. The recommended dose is 4.5 mg/m2/dose once daily, for up to 2 years or until progression or unacceptable toxicity.

The primary endpoint is objective response rate, based on complete and partial response definitions, with a 2-year timeframe. The record does not report the primary endpoint result, its denominator, or an uncertainty interval. It lists secondary outcomes related to response duration, survival, safety, and biomarkers, but does not report their analysis results.

Adverse-event information lists one participant with a serious adverse event, 0 with other adverse events, pneumonia at 9.1% among the top serious terms, and 10 deaths. Timing, causes, and treatment relationships are not reported in the registry record. The design and available results do not support a randomized comparison.