Sunitinib Malate in Treating Younger Patients With Recurrent, Refractory, or Progressive Malignant Glioma or Ependymoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sunitinib Malate in Treating Younger Patients With Recurrent, Refractory, or Progressive Malignant Glioma or Ependymoma (NCT01462695), a non-randomized phase 2 study. The primary outcome is Sustained Objective Response Rate.

2. Clinical Question

3. Trial Design

This was a phase II, non-randomized, single-group study sponsored by the National Cancer Institute (NCI). The registry records an enrollment of 30. That is the enrollment figure, not a response-evaluable count: the record specifically states that one patient in Stratum A did not receive study drug and was excluded from response evaluation. No randomized allocation or masking was used.

The study addressed recurrent, refractory, or progressive malignant glioma or ependymoma in pediatric and young adult patients. Its named groups were Stratum A, recurrent high-grade glioma, and Stratum B, recurrent ependymoma. These disease strata allow outcomes to be described by tumor group, but they do not create a controlled treatment comparison. Differences between groups could reflect their underlying diseases or other group characteristics; the registry record does not report an adjustment strategy to account for such differences.

Patients received sunitinib malate orally once daily on days 1-28. The schedule repeated every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. These are planned treatment instructions, not evidence that every participant received the full schedule or completed the maximum number of courses.

The recorded study start is 2012-01 and primary completion is 2013-12; the status is completed. The primary outcome timeframe is listed as up to 5 years. The registry record does not report the details of assessment timing within that timeframe, the actual duration of follow-up for each patient, or the extent of treatment exposure. These omissions limit what can be inferred about how completely the planned assessment and treatment schedule was carried out.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: One patient in Stratum A was excluded because the patient did not receive study drug and therefore was not evaluable for response.

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 Sustained Objective Response Rate, measured over Up to 5 years.

The primary endpoint was sustained objective response rate, expressed as a percentage of patients. It combines complete and partial responses, but only when the response lasts at least 8 weeks. A partial response required at least a 50% decrease in the sum of the products of the perpendicular diameters of target lesions, with initial baseline measurements as the reference; the definition allowed up to 5 target lesions. A complete response required disappearance of all target lesions.

This endpoint is used to describe whether measurable tumors show a substantial decrease or disappear for a specified duration. Requiring a response to last at least 8 weeks distinguishes a sustained response from a brief change. As a general statistical point, a percentage is a summary of the frequency of an outcome in a defined analysis population; it does not, by itself, show how long patients lived, how symptoms changed, or how outcomes compare with an untreated or alternative-treatment group.

The registry lists the endpoint and a timeframe of up to 5 years, but does not report the observed response percentage or its 95% confidence interval. It also notes that one patient in Stratum A did not receive study drug and was not evaluable for response. The registry record does not report further details about response assessments or how incomplete observations were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design determines what statistical conclusions can be drawn. This study is listed as non-randomized and single-group, with no masking. In a randomized controlled trial, random assignment is intended to make treatment groups comparable on average, so a difference in outcomes can be interpreted as a treatment contrast under the design's assumptions. That logic does not apply: there is no randomized control group. The study can describe response and adverse events among treated participants, but it cannot isolate a treatment effect by comparing outcomes against a concurrent control.

What does the response percentage represent?

A response rate is the proportion of an analysis population meeting a prespecified response definition. Here, the endpoint is a sustained objective response, combining complete and partial responses lasting at least 8 weeks. The partial-response criterion uses tumor measurements relative to initial baseline, and the complete-response criterion is disappearance of all target lesions. The outcome is therefore not simply any change in tumor size; it depends on the stated measurement thresholds, target-lesion rules, and duration criterion.

The registry record gives the endpoint definition but not its observed percentage. It also does not report the response denominator or the 95% confidence interval. As a general statistical explanation, a confidence interval describes a range of values compatible with the data under a specified method and its assumptions. It communicates uncertainty around an estimate; it is not a guarantee that the true value falls in that range. Without the estimate and interval, neither the response frequency nor the precision of that estimate can be evaluated from the posted results.

Why does the analysis population matter?

An outcome rate depends on who is included in its denominator and how participants with missing or unevaluable outcomes are handled. The record says one patient in Stratum A was excluded because that patient did not receive study drug and was therefore not evaluable for response. This documents one reason for exclusion, but does not provide a complete accounting of response populations or missing assessments. The enrollment of 30 should not be substituted for a response denominator unless the registry explicitly identifies it as such, which it does not.

In general, excluding participants can affect an estimate if the reason for exclusion is related to prognosis or the chance of observing an outcome. Different analysis populations can answer different questions: for example, one may describe outcomes among those who started treatment, while another may retain everyone enrolled. The registry record does not report which analysis population was used for the primary response estimate, or how any other missing or unevaluable outcomes were treated.

What do the strata allow?

Stratum A is recurrent high-grade glioma and Stratum B is recurrent ependymoma. Reporting outcomes separately by disease group can make a descriptive result more clinically interpretable when the enrolled conditions differ. However, the strata are not a randomized comparison. General statistical practice cautions against treating differences between groups with distinct conditions as evidence that the treatment has different effects, because group membership is associated with the disease being studied and may be associated with other prognostic factors. The registry record does not report adjusted comparisons between strata.

How should planning calculations be read?

The sample-size planning illustrations are described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses a total number of events; for other outcomes it gives participants per arm. These are general planning calculations, not descriptions of the actual single-group trial design. They should not be read as observed power or as evidence that the trial was designed with those assumptions. The registry record does not report a sample-size justification for the study's actual design.

More generally, a significance level is a threshold used in a testing procedure to control the probability of a specified type of false-positive conclusion under the null model and assumptions. A two-sided test allows departures in either direction. A normal approximation uses a mathematical distribution to approximate the sampling behavior of an estimator. These concepts explain the stated planning assumptions; they do not supply an analysis of the trial outcome.

What does the safety summary measure?

The serious adverse-event summary lists participants at risk and affected within each stratum, while selected event terms are accompanied by percentages. These are descriptive counts and percentages. As a general statistical point, event terms can overlap within a participant, so listed terms should not be assumed to represent mutually exclusive categories unless the record says so. The registry record does not specify a comparative safety analysis, and the single-group design supplies no concurrent control risk against which to assess these figures.

Overall, statistical interpretation depends on both the numerical estimate and its analysis context. The posted record gives design and endpoint definitions, but the primary response estimate, confidence interval, detailed analysis population, and statistical plan are not reported in the registry record. Those omissions constrain evaluation of the endpoint beyond its intended definition.

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("Stratum A: Recurrent High Grade Glioma", "Stratum B: Recurrent Ependymoma")
n      <- c(16, 13)
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  Stratum A: Recurrent High Grade Glioma  16  0  0.0  0.0  20.6  0.0  19.4  0.1  19.5
ARM  Stratum B: Recurrent Ependymoma  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is identified as sustained objective response rate, but the registry record does not report a statistical analysis plan. It does not state whether there were multiple primary hypotheses, how secondary outcomes were tested, or whether any adjustment for multiple testing was planned. The record also does not report interim analyses or stopping rules. These items are not reported in the registry record, so their presence or absence in the study's conduct should not be inferred.

Missing-data handling is also not reported. The record documents that one patient in Stratum A did not receive study drug and was excluded from response evaluation. It does not provide a full accounting of participants with missing or unevaluable response assessments, reasons for any such cases, or the methods used to address them. As a general statistical point, response rates can depend on whether participants without an evaluable outcome are excluded, counted as not responding, or handled by another prespecified method. The choice should be known to interpret the estimate, but is not reported.

The enrollment figure of 30 is not a substitute for an analysis denominator. The registry does not report a complete response-evaluable count by stratum, nor does it state which population was used for the primary endpoint analysis. The posted results also do not include the response estimate or its confidence interval. Accordingly, the effects of missingness, exclusions, or any multiplicity procedure cannot be assessed from the registry record.

General statistical reporting practice favors clear identification of the analysis population, missing-outcome rules, and multiplicity strategy, because those choices affect interpretation of uncertainty and false-positive risk. These 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.

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: neoplasms benign, malignant and unspecified (incl cysts and polyps) - other (43.8%), death nos (37.5%), seizure (18.8%), hydrocephalus (12.5%), intracranial hemorrhage (12.5%).

The serious adverse-event summary is divided into Stratum A, recurrent high-grade glioma, and Stratum B, recurrent ependymoma. For Stratum A, the record lists 16 participants at risk and 14 affected by serious adverse events; for Stratum B, it lists 13 at risk and 9 affected. For other adverse events, the corresponding entries are 16 at risk and 8 affected in Stratum A, and 13 at risk and 6 affected in Stratum B. These are descriptive figures for the strata, not a comparison with a control group.

The registry also lists serious-event terms with percentages: neoplasms benign, malignant and unspecified (including cysts and polyps) - Other, 43.8%; Death NOS, 37.5%; seizure, 18.8%; hydrocephalus, 12.5%; intracranial hemorrhage, 12.5%; and gait disturbance, 7.7%. The record does not report stratum-specific percentages for these terms. It does not explain whether participants could appear under multiple terms, so the entries should not be added or treated as mutually exclusive categories.

These figures do not establish causation or comparative risk. Details such as event timing, duration, severity grading, attribution to treatment, and the handling of recurrent events are not reported in the registry record. Death NOS is an event term in the serious-event listing; the record does not provide further detail that would support interpreting it as a cause-of-death result.

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

The record defines a study of sunitinib malate in younger patients with recurrent, refractory, or progressive high-grade glioma or ependymoma, and specifies a sustained objective response endpoint. However, it does not report the endpoint's observed percentage or its 95% confidence interval. The registry therefore does not provide the numerical primary result needed to describe how often sustained responses occurred or how precise that estimate was.

Even if an outcome estimate were available, the study's non-randomized, single-group design would shape its interpretation. A response percentage among treated participants is descriptive. Without a concurrent randomized comparator, it cannot show how the outcome would have differed under another treatment or no treatment. Stratum A and Stratum B are different disease groups, not control and intervention arms.

The endpoint has a specific meaning: partial or complete tumor response sustained for at least 8 weeks. It is not a general measure of every aspect of disease status, quality of life, survival, or treatment burden. The registry record does not report results for those outcomes in the posted primary endpoint information. The defined timeframe of up to 5 years does not, by itself, establish how long each participant was followed or what assessments were completed.

The adverse-event figures describe counts and selected terms in the two strata, but do not supply a controlled comparison or all details needed to assess event attribution and timing. They are not a complete characterization of treatment safety. The record also does not report the analysis population, missing-data methods, multiplicity procedures, or a full statistical analysis plan.

Accordingly, the posted information establishes the study's question, design, treatment schedule, endpoint definition, and selected safety summaries. It does not establish a primary response result, comparative treatment effect, or the precision of an effect estimate. Any conclusions beyond those boundaries would require information not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clearly defined endpoint and a reported result. The registry specifies sustained objective response and gives the criteria for partial and complete response, including the requirement that a response last at least 8 weeks. Yet the response estimate and confidence interval are not reported in the registry record. An endpoint definition tells readers what was intended to be measured; it cannot replace the outcome data needed to evaluate what was observed.

The design also illustrates why the comparison structure matters. A non-randomized, single-group study can describe outcomes in the treated cohort, but it does not create a randomized estimate of the difference between treatment strategies. The two disease strata may be useful for organizing descriptive results, while still being unsuitable as a like-for-like control comparison. Statistical interpretation must respect that distinction.

The record's explicit note about a patient who did not receive study drug and was excluded from response evaluation highlights the importance of defining the analysis population. Enrollment and evaluability are not interchangeable concepts. A response rate is interpretable only when its denominator and the handling of missing or unevaluable outcomes are clear. Those details are not fully reported in the registry record.

Finally, the safety summary shows how event counts and selected percentages can inform description without establishing causation or comparative risk. A single-group record can report what was recorded in participants, but the absence of a concurrent control limits comparative interpretation. Together, these features make the record a useful reminder that endpoint definitions, design, denominators, precision, and reporting completeness all contribute to statistical meaning.

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 primary limitation for interpreting efficacy is that the registry record does not report the sustained objective response rate or its 95% confidence interval. The endpoint is defined, but the observed value and its precision are unavailable. The record also does not provide a complete response-evaluable denominator by stratum, so the enrollment figure cannot be used to reconstruct the rate.

The single-group, non-randomized design has no concurrent comparator. Consequently, the posted information cannot establish a treatment contrast, and comparisons between the two strata would involve different tumor groups rather than like-for-like arms. No adjustment strategy for possible differences between strata is reported.

Response evaluation has one documented exclusion: one patient in Stratum A did not receive study drug and was not evaluable for response. The registry record does not report further detail on missing or unevaluable response assessments, the handling of missing outcomes, or the analysis population used for the primary endpoint. The extent to which the planned follow-up timeframe of up to 5 years was achieved is also not reported.

The statistical analysis plan, multiplicity procedures, interim analyses, and sample-size justification for the actual study design are not reported in the registry record. The planning illustrations use assumptions that differ from the single-group design, including equal allocation between two arms; they should not be treated as the study's observed design or as observed power.

The safety summaries are limited to listed counts and selected serious-event terms. Timing, duration, severity grading, treatment attribution, and participant overlap across terms are not reported. These gaps restrict interpretation of the safety information and prevent controlled comparisons of event risk.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sunitinib Malate in Treating Younger Patients With Recurrent, Refractory, or Progressive Malignant Glioma or Ependymoma — NCT01462695.
• Registry record last updated 2015-08-27; status last verified 2015-06.
• Results first posted 2015-03-23.
• 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 study sponsored by the National Cancer Institute (NCI), with a recorded start of 2012-01 and primary completion of 2013-12. It lists enrollment of 30 and a non-randomized, unmasked, single-group design. The study concerned pediatric and young adult patients with recurrent, refractory, or progressive high-grade glioma or ependymoma, with strata for recurrent high-grade glioma and recurrent ependymoma.

The treatment schedule was oral sunitinib malate once daily on days 1-28, repeating every 42 days for up to 18 courses unless progression or unacceptable toxicity occurred. The primary endpoint was sustained objective response rate, with a timeframe of up to 5 years. The registry record does not report the primary response estimate, confidence interval, full analysis population, or statistical analysis plan. It does report selected adverse-event counts and terms, which are descriptive and have no randomized control comparison.