Sorafenib in Children and Young Adults With Recurrent or Progressive Low-Grade Astrocytomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sorafenib in Children and Young Adults With Recurrent or Progressive Low-Grade Astrocytomas (NCT01338857), a na phase 2 study. The primary outcome is Response Rate to Sorafenib.

2. Clinical Question

3. Trial Design

This was a phase II, single-group study sponsored by NYU Langone Health. The registry lists an enrollment of 12, no masking, and no randomized allocation. Sorafenib was the only intervention listed. Without a separate control group, the design focuses on outcomes observed among participants receiving the study treatment rather than a direct comparison between treatment groups.

The registry records a start date of 2011-04 and a primary completion date of 2013-03. Its status is terminated. The reason for termination is not reported in the registry record, so the status alone does not explain why the study ended or whether the decision was related to safety, recruitment, efficacy, or another consideration.

The treatment description specifies oral administration twice daily, approximately every 12 hours. Each cycle was 28 days, with no interruption between cycles, and participants could receive up to 12 cycles if they remained on protocol. The description also states that grapefruit juice was not allowed while taking sorafenib.

The primary endpoint was intended to estimate objective response over one year. The record states that the study terminated and that 1/12 participants completed and data was analyzed. It does not report the observed response count or rate, the response assessment criteria, or the analysis method. Although the study description includes optional genetic testing, the registry record does not report genetic-analysis results.

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: Participants were not excluded from the trial before assignment to groups. Treatment was based on age and diagnosis of neurofibromatosis type I.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Study terminated and 1/12 participants completed and data was analyzed

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 Response Rate to Sorafenib, measured over one year.

The primary endpoint is titled “Response Rate to Sorafenib.” Its stated purpose is to estimate objective response rates in children and young adults with low-grade astrocytomas, including optic pathway gliomas, over one year. The outcome is represented as a number of participants, but the registry record does not give the response count, response rate, or criteria used to classify a response.

In general, an objective response endpoint records whether participants meet specified criteria for a measurable reduction in disease. A response rate summarizes the proportion of an assessed group meeting those criteria. This kind of endpoint can describe tumor response within a treated group; by itself, it does not establish how outcomes would compare with a different treatment or with no study treatment. The precise interpretation depends on the assessment rules, timing, and analysis population.

The registry record says that 1/12 participants completed and data was analyzed, but does not clarify how that statement relates to the primary endpoint denominator. It also does not report whether response assessments were available for other participants. As a result, the intended endpoint can be described, but its observed value and precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study describes outcomes among participants who receive the intervention. For a binary endpoint, each assessed participant is classified according to whether the endpoint occurred, and the response rate summarizes the share of the assessed group meeting the response definition. This summary is meaningful only alongside a clear response definition, a defined analysis population, and adequate information about missing assessments. Those details are not reported in the registry record for this endpoint.

This study is listed as single-group, with allocation not applicable and no masking. That design can address the stated aim of estimating objective response among treated participants, but it does not create a concurrent comparison with another treatment. A difference between an observed outcome and an expectation from elsewhere would not be a randomized treatment effect. No external comparison or adjustment approach is reported in the registry record.

How should a response rate be read?

In general, a response rate is a proportion: its numerator is the number meeting the response criteria, and its denominator is the number included in the analysis. The denominator might be defined by enrollment, treatment initiation, or availability of an evaluable assessment, depending on the protocol and analysis plan. The registry record does not state the response criteria or analysis-population rule. It reports that 1/12 participants completed and data was analyzed, but that statement alone does not identify the endpoint numerator or denominator.

A confidence interval, in general, describes the range of values compatible with the observed data under a specified statistical procedure. For a response rate, it can convey uncertainty associated with the finite number of assessed participants. No confidence interval is reported for this endpoint, and no primary response estimate is posted. Precision therefore cannot be judged from a reported interval or reconstructed from the completion statement.

What can the analysis record tell us?

The registry record lists no analyses. It does not report a statistical test, a model, an adjustment strategy, an interim analysis, or a statistical analysis plan. These items are distinct from the endpoint’s stated purpose: saying that the study aimed to estimate a response rate does not specify how the estimate was calculated or how uncertainty was handled. Details such as response-assessment timing, handling of unevaluable participants, and treatment of missing outcome data are also not reported in the registry record.

In general, methods for binary outcomes should match the design and the way the endpoint is collected. When observations are not independent, or when outcomes cluster in groups, methods that account for that structure may be needed; over-dispersion is one possible concern in some models for grouped or count data. The registry record does not describe clustered observations, a count model, or over-dispersion, so these are general considerations rather than methods attributed to this trial.

How do the planning assumptions relate to the study?

The record describes sample-size planning illustrations using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with effects framed as stated fractions of an observed effect. These are planning assumptions, not a description of the enrolled study’s single-group design. The registry record does not report a trial-specific sample-size justification, the observed effect used for the illustrations, or a power calculation for this study. Any such illustration is not observed power and should not be interpreted as evidence that the trial had a particular probability of detecting an effect.

In general, a planning calculation asks what sample size might be needed under selected assumptions about an effect and statistical procedure. It does not show what the study actually found, and it does not replace a reported estimate with uncertainty. Here, the record’s enrollment and completion information cannot be used to infer an endpoint result or to validate the planning assumptions.

Why does the design matter for inference?

Random assignment in a controlled study is one way to make groups comparable on average, including with respect to factors that are not fully measured. This study has no randomized comparator group, so it cannot use that design-based protection for a treatment contrast. A response observation in a single group may be useful descriptively, but the registry record does not provide the comparison needed to distinguish treatment-associated outcomes from other explanations.

In general, statistical significance and clinical importance are different questions. A significance test evaluates data relative to a specified statistical model and null hypothesis; clinical importance concerns the practical meaning of the effect. Neither can be assessed without an observed effect estimate and sufficient methodological detail. Since no primary response result or inferential analysis is reported in the registry record, neither statistical significance nor the size and precision of an effect can be characterized.

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("Sorafenib (Nexavar)")
n      <- c(1)
events <- c(1)
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  Sorafenib (Nexavar)  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures, but only the primary response-rate aim is described in the available endpoint information. The identity and results of any additional outcome are not reported in the registry record. The study description also mentions tolerability and optional analysis of tumor genetic makeup, but it does not provide corresponding analysis results.

Multiplicity concerns arise in general when several outcomes, time points, subgroups, or statistical tests are examined. If many tests are conducted, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. The registry record does not report a multiplicity strategy, a hierarchy among outcomes beyond identifying the primary endpoint, or a complete statistical analysis plan. Because no analyses are listed, the record does not establish which comparisons or tests were actually performed.

Missing-data handling is also not reported. The completion statement says that 1/12 participants completed and data was analyzed, but it does not explain why other participants did not complete, whether their endpoint data were missing, or how any missing assessments were handled. It is not possible to assume that all participants without a completion designation lacked outcome data, or that incomplete participation had a particular cause.

The analysis population is not defined in the registry record. It does not state whether the primary endpoint was analyzed among all enrolled participants, participants who began treatment, participants with an assessment, or another group. These omissions prevent assessment of how participant exclusions or incomplete follow-up might affect the response estimate.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry safety figures list 12 participants at risk for serious adverse events, with 0 affected. For other adverse events, 12 participants were at risk and 12 were affected. These are participant counts as recorded, not a description of the total number of separate events or how often events occurred over time.

The record does not list serious adverse-event terms. It also does not report event timing, duration, severity details beyond the serious/other categories, or whether investigators considered events related to sorafenib. The deaths figure is not reported in the registry record. A zero count for the posted serious-event category should be read as the registry’s reported count for that category, not as evidence that no health events of any kind occurred.

Because the study has no comparator group and the registry provides no event-level details, these figures cannot establish comparative safety or characterize the full pattern of adverse events. The record’s small enrollment and limited completion information further constrain interpretation. The counts describe what was posted for participants at risk; they do not support a broader conclusion about safety.

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

The study was designed to estimate objective response to sorafenib in children and young adults with recurrent or progressive low-grade astrocytomas, including optic pathway gliomas. The registry record establishes the intended endpoint and records an enrollment of 12. It also says that the study terminated and that 1/12 participants completed and data was analyzed.

Those details do not provide the primary response result. The registry record does not report the number of participants who responded, the estimated response rate, the criteria used to determine response, or an uncertainty interval. Accordingly, the posted information cannot show the size or precision of an observed response estimate. It also cannot establish whether the result met any prespecified statistical threshold, because a threshold and test result are not reported.

The single-group design means there is no concurrent control group for a direct treatment comparison. Even if a response estimate were available, it would describe outcomes in the assessed study group rather than, by itself, establish what would have happened under an alternative. The registry record does not report methods that would support a controlled comparison.

The safety record reports 0 serious adverse events among 12 at risk and other adverse events among 12 at risk. This is a descriptive account of posted counts; event terms and further details are not reported. The record also does not report the reason for termination, so the status should not be interpreted as evidence of a particular safety or efficacy finding.

The trial description includes optional tumor genetic testing, but the registry record does not report genetic-analysis results. The available information therefore supports conclusions about the trial’s structure and the limits of its posted results, not a conclusion about response, comparative benefit, or genetic predictors.

14. Why This Trial Matters Statistically

This trial illustrates why design details and outcome reporting need to be read together. The registry identifies a specific clinical question—estimating objective response over one year—but the posted record does not include the corresponding response count or estimate. A stated aim is not a result, and enrollment alone cannot supply the missing endpoint information.

The single-group structure is another central statistical feature. It can describe outcomes among treated participants, but it does not offer a randomized comparison with another treatment. This distinction matters whenever readers consider whether an observed outcome can be attributed to an intervention rather than simply described in a group that received it.

The completion statement also demonstrates the importance of analysis-population reporting. The registry says 1/12 participants completed and data was analyzed, but does not explain how endpoint availability, completion, and analysis relate to one another. Without that information, readers cannot determine the denominator behind a response estimate—even if an estimate were posted.

Finally, the record separates several different kinds of evidence: an intended response endpoint, adverse-event counts, an optional genetic aim, and planning assumptions. These cannot be substituted for one another. The safety counts do not answer the response question, and planning illustrations do not show what was observed. Clear reporting of outcomes, uncertainty, analysis populations, and reasons for study termination is essential for interpreting a clinical trial statistically.

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 limitation in interpreting the results is that the primary response outcome is not reported. The registry record gives the endpoint’s purpose and timeframe, but not the response count, rate, assessment criteria, or uncertainty. Without those details, the central efficacy estimate cannot be evaluated.

The study was single-group and had no randomized comparator. This prevents a direct, controlled treatment comparison. The record also lists an enrollment of 12 and states that 1/12 participants completed and data was analyzed, but does not explain participant flow or define the analysis population. The reason for termination is not reported in the registry record.

Further methodological details are absent: the statistical analysis plan, handling of missing data, response-assessment procedures, and any interim analyses are not reported in the registry record. The registry lists two outcome measures, but information sufficient to describe all outcomes and their results is not available. No analyses are listed.

The optional genetic-testing aim required available tumor tissue, but the registry record does not report how many participants had testing or any genetic findings. Safety reporting is also limited to participant counts, without serious-event terms, event-level descriptions, or a reported deaths figure. These limitations restrict interpretation to the design and posted counts rather than conclusions about response, comparative outcomes, or genetic associations.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sorafenib in Children and Young Adults With Recurrent or Progressive Low-Grade Astrocytomas — NCT01338857.
• Registry record last updated 2017-02-17; status last verified 2016-12.
• Results first posted 2016-02-22.
• 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

NCT01338857 is a phase II, single-group study of sorafenib (Nexavar) in children and young adults with recurrent or progressive low-grade astrocytomas, including optic pathway gliomas. NYU Langone Health is listed as sponsor. The record gives a start date of 2011-04, a primary completion date of 2013-03, an enrollment of 12, and a status of terminated.

The primary endpoint was intended to estimate objective response over one year. The registry states that 1/12 participants completed and data was analyzed, but does not report the response result or analysis method. The safety figures record 0 serious adverse events among 12 at risk and other adverse events among 12 at risk. The reason for termination, deaths, and genetic-analysis findings are not reported in the registry record.