Pilot Study of Cabozantinib for Recurrent or Progressive Central Nervous System Tumors in Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study of Cabozantinib for Recurrent or Progressive Central Nervous System Tumors in Children (NCT02885324), a na phase 2 study. The primary outcome is Number of Participants With Disease Response.

2. Clinical Question

This clinical question is exploratory rather than comparative. The registry record identifies the intended population, the cabozantinib regimen, and the response assessment timeframe, but it does not provide enough outcome information to establish how many participants met any response category. Nor does it report a control group that could help distinguish treatment-associated change from the course of disease or other influences. Interpretation must therefore remain tied to the stated aims and the information actually recorded.

3. Trial Design

The registry identifies this as a phase 2 pilot study of cabozantinib for recurrent or progressive central nervous system tumors in children. The design is single group, with no masking and allocation listed as not applicable. Enrollment is recorded as 4. The study status is terminated. The registry record gives a start date of 2017-05-18 and a primary completion date of 2020-08-25; it does not report why the study was terminated.

Participants in the cabozantinib group were described as taking the drug daily at 40 mg/m2. Treatment cycles were to last 28 days and continue for up to 12 months of therapy on study. These are regimen details, not evidence that every participant received the intended duration or dose. Treatment exposure and adherence are not reported in the registry record.

The brief summary frames the study as examining feasibility and exploratory efficacy in recurrent or refractory central nervous system tumors for which there are no curative options. It also names safety, time to progression, event free survival, and overall survival as areas of follow-up. The listed secondary outcomes are overall survival and the number of participants with progression free survival. The registry record does not report further details about follow-up procedures, outcome assessment schedules beyond the primary endpoint timeframe, or how the study was conducted after enrollment.

Because this is a single-group study, any outcome count would describe the observed group rather than an effect relative to a concurrent control. The design does not support a randomized comparison, and the record explicitly notes that the arms are not a like-for-like control comparison. With enrollment recorded as 4, the study is a small pilot, but the record does not state a formal sample-size justification or explain whether the enrollment reflected a target or the final number enrolled.

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 Number of Participants With Disease Response, measured over 6 months.

The primary endpoint is the number of participants with disease response at 6 months. It is a count endpoint: it describes how many participants are assigned to response categories at the stated assessment time, rather than measuring an average change in a continuous quantity. The registry description identifies complete response, partial response, stable disease, and progressive disease as best-response categories. It does not state the observed count in any category, so the primary result cannot be quantified from the registry record.

Response is assessed using the product of the longest diameter of a lesion and its longest perpendicular diameter. Complete response is defined as disappearance of all target lesions. Partial response requires at least a 50% decrease in the sum of the products of the two perpendicular diameters of target lesions, using the initial baseline measurements as the reference. Stable disease is neither enough decrease to qualify as partial response nor enough increase in a single target lesion to qualify as progressive disease. Progressive disease is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

A response endpoint can provide a structured way to describe tumor status at a specified follow-up time. The record’s inclusion of stable disease and progressive disease alongside complete and partial response means the named endpoint encompasses several distinct clinical states; the count alone would need category-level context to show how participants were distributed. The registry record does not explain whether the categories were combined for the reported primary result, nor does it report the response count or its uncertainty. This outcome is also distinct from time-to-event outcomes such as overall survival or progression-free survival.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information available for this study is limited. The registry describes a single-group design, identifies a count-based primary endpoint, and lists secondary outcomes. It records no analyses. A statistical analysis plan, including specified estimands, model choices, handling of incomplete observations, or inferential procedures, is not reported in the registry record. The explanations below describe general statistical concepts and do not imply that those methods were used in this study.

What does a count endpoint represent?

A count endpoint records the number of participants in a defined outcome category or set of categories. The primary outcome is phrased as the number of participants with disease response at 6 months, with response criteria covering complete response, partial response, stable disease, and progressive disease. A count is most interpretable when the outcome categories, assessment time, and denominator are clear. The registry record gives the assessment time and definitions, but it does not report the observed counts or state the analysis population used for the endpoint. The phrase “number of participants with disease response” also needs care because the listed categories include progressive disease; without a reported category breakdown or a rule for combining categories, the intended summary cannot be reconstructed.

What does a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimate under the assumptions of the statistical method used. For a count-based outcome, an analysis might report a proportion and an interval, but no such estimate or interval is reported in the registry record. An interval would not resolve the limitations of a single-group design: it can describe uncertainty around an observed group result, but it cannot create a randomized comparison or eliminate bias from selection, follow-up, or other sources.

Why does the design matter for inference?

In general, randomized comparative designs can support estimation of differences between groups when allocation and analysis are appropriate. Here, the registry records a single group, no masking, and allocation as not applicable. There is no concurrent comparator in the recorded design. Therefore, a treatment-versus-control contrast is not available from this study’s design. A within-group response count can be descriptive, but attributing an outcome to the intervention requires evidence beyond observing the group’s status.

What can the sample-size illustrations mean?

The sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a specified fraction of the observed effect. For time-to-event illustrations, the stated quantity is the total number of events; for other illustrations, it is participants per arm. These are planning assumptions, not the trial’s recorded design: the trial itself is single group. Such illustrations are hypothetical sample-size calculations, not observed power and not evidence that the study was designed with those assumptions. No numerical planning results or underlying observed effect are reported in the registry record, so the illustrations cannot be used to establish a specific enrollment target or achieved precision.

In general, a sample-size calculation depends on the outcome, target effect, variability or event rate, significance level, power target, allocation, and analysis method. If any of these assumptions differs from the eventual study, the planning result may not describe the study’s actual ability to estimate an effect. In a pilot, feasibility aims may also be relevant, but the registry record does not report a formal sample-size justification or specify a feasibility threshold.

Why can over-dispersion matter?

In general, over-dispersion occurs when count data vary more than a chosen statistical model expects. If an analysis assumes less variability than is present, standard errors can be too small and intervals or tests can be misleading. A model that allows extra variability may be appropriate in some count settings, but the choice depends on the outcome and data structure. The primary outcome is described as a participant count, and no model or dispersion estimate is reported. There is therefore no basis for saying that over-dispersion was assessed or that a particular model was used.

What is the role of time-to-event methods?

Overall survival and progression-free survival are time-to-event concepts: they concern time from a defined origin to an event, with participants who have not experienced the event by their last observation typically handled as censored. In general, valid interpretation depends on clear event definitions, an origin date, follow-up, censoring rules, and an analysis method. The registry lists overall survival and a count of participants with progression free survival, but it does not report event definitions, follow-up summaries, censoring details, or outcome analyses. Event free survival and time to progression appear in the brief summary as follow-up interests, but are not listed among the named secondary outcomes. The record does not provide results for these measures.

These general concepts clarify what further information would be needed to interpret estimates, but they do not fill gaps in the registry record. With no reported primary outcome count, no analyses, and no stated statistical plan, inferential conclusions cannot be reconstructed from the design description alone.

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("Cabozantinib")
n      <- c(4)
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  Cabozantinib  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 3 outcome measures. It identifies disease response at 6 months as the primary outcome and lists overall survival and the number of participants with progression free survival as secondary outcomes. The brief summary additionally mentions safety, time to progression, and event free survival as follow-up interests. The record does not explain how these aims relate to the listed outcome measures or identify which outcomes were formally analyzed.

When multiple outcomes or repeated statistical tests are assessed, the chance of at least one apparently notable result can increase. In general, a prespecified hierarchy, adjustment procedure, or clearly exploratory interpretation can help readers understand multiplicity. No multiplicity strategy or statistical analysis plan is reported in the registry record. The record lists no analyses, so there are no reported tests or estimates for which to assess multiplicity handling.

Missing-data methods and analysis populations are also not reported in the registry record. It does not state how unavailable assessments, withdrawal, incomplete follow-up, or participants who did not complete treatment were handled. Nor does it specify whether the primary outcome used all enrolled participants, participants who received treatment, or a different defined population. The enrollment entry and adverse-event counts do not answer those questions for the efficacy endpoints. Without this information, the completeness and denominator of any outcome analysis cannot be assessed. No missing-data method should be assumed.

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 non-serious adverse event terms

The registry’s adverse-event entries list 4 participants at risk for serious adverse events and 0 affected by serious adverse events in the cabozantinib group. For other adverse events, it lists 4 at risk and 4 affected. The record also reports 2 deaths. These entries are counts, not estimates of comparative risk, and there is no control group against which to compare them.

The serious-event entry indicates that no affected participants are recorded in that category; it does not establish that serious events were impossible or that the treatment is safe. The “other adverse events” entry indicates that all 4 at-risk participants were recorded as affected in that category, but the record does not give the event terms or number of events per participant. The death count is not accompanied by a cause or a statement of relationship to cabozantinib. Timing, follow-up duration for safety, severity details, and event attribution are not reported in the registry record.

These figures should therefore be read as descriptive registry counts only. They do not permit assessment of comparative safety, the nature of the events, or whether deaths were related to study treatment.

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

The registry record documents a phase 2 pilot study of daily cabozantinib for children with recurrent or progressive central nervous system tumors. It gives the intended regimen, names a six-month disease-response endpoint, and describes the response categories. It also records enrollment as 4 and the study status as terminated. Those details establish the study’s stated scope, but they are not efficacy findings.

The record does not report the primary response count or category-specific results. It also does not report analyses for the secondary outcomes. Accordingly, the posted information does not show how many participants had complete response, partial response, stable disease, or progressive disease, and it cannot quantify the precision of an outcome estimate. The registry record does not support a conclusion about the size or direction of an efficacy effect.

Even with complete outcome counts, a single-group pilot would describe observed outcomes without a concurrent control comparison. That design cannot separate treatment-associated outcomes from other possible explanations as a randomized comparison can. The record does not give enough information about participant characteristics, treatment exposure, or outcome completeness to resolve those issues.

The safety counts are also descriptive. They record 0 affected participants for serious adverse events, 4 for other adverse events, and 2 deaths, but the registry does not report event details or treatment relationship. These entries cannot establish that cabozantinib caused or did not cause a particular event.

The study’s exploratory aims and pilot designation are important context: they identify an investigation intended to examine feasibility and exploratory efficacy, not a definitive comparative claim. The reported record supports description of the design and its recorded counts, while the primary and secondary efficacy results, analysis methods, and reasons for termination remain unreported.

14. Why This Trial Matters Statistically

This study illustrates why a registry entry needs to be read in layers. The design identifies what comparison is possible; the endpoint definition clarifies what was intended to be measured; and the reported outcome results determine what can actually be concluded. Here, the record describes a single-group pilot, a six-month disease-response count, and lesion-based response criteria, but does not report the primary outcome count or any analyses. The distinction between a planned measure and an observed result is therefore central.

The study also shows why a response endpoint needs clear category-level interpretation. The definition includes complete response, partial response, stable disease, and progressive disease, which represent different clinical states. A single count described as participants with disease response would be difficult to interpret without knowing which categories contributed to it. The registry record gives the category definitions but not the reported distribution or a rule for combining categories.

Small pilot studies can have value for feasibility and exploratory questions, but the enrollment recorded as 4 limits the scale of what the record can describe. It is not a basis for inferring precision or a treatment effect, especially without reported outcome estimates and analysis details. The lack of a comparator further limits causal interpretation.

Finally, the adverse-event counts demonstrate the difference between a count and a safety conclusion. Counts are useful to document what the record says was observed, but without event details, timing, attribution, and comparison, they do not answer whether events were caused by treatment. Clear registry reporting of outcomes, denominators, analysis populations, and methods is essential for readers to distinguish a descriptive pilot record from evidence of comparative benefit or harm.

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.

Several limitations are specific to the information recorded for this study. First, the primary endpoint is defined, but its observed count is not reported. The registry record therefore does not show how the participants were classified at 6 months. It also does not provide an outcome breakdown across the response categories, despite defining each category.

Second, the study is single group, with no masking and no comparator. There is no randomized control comparison to support an estimate of relative effect. The record does not report a protocol-level explanation for these design choices or a formal sample-size justification. The reason for termination is also not reported in the registry record.

Third, enrollment is recorded as 4, while the record does not state the analysis population for efficacy outcomes or whether outcome assessments were available for everyone enrolled. Treatment exposure, dose changes, adherence, discontinuation, and reasons for stopping treatment are not reported. These omissions make it difficult to understand how closely the delivered regimen matched the intended daily dosing schedule and treatment duration.

Fourth, secondary outcome results and analysis methods are absent. Follow-up details for overall survival and progression-free survival, including event definitions and censoring, are not reported. The record also does not explain the relationship between the brief summary’s follow-up interests and the named outcome measures. Statistical methods, multiplicity handling, and missing-data methods are not reported in the registry record.

Finally, safety entries lack event terms, timing, severity detail beyond the broad serious/other grouping, and attribution. The death count has no stated cause or relationship to treatment. These limits mean the counts cannot support detailed safety conclusions, just as the missing efficacy analyses prevent conclusions about the primary outcome.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pilot Study of Cabozantinib for Recurrent or Progressive Central Nervous System Tumors in Children — NCT02885324.
• Registry record last updated 2022-10-06; status last verified 2022-10.
• Results first posted 2022-08-15.
• 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 phase 2, single-group, unmasked pilot study of cabozantinib for children with recurrent or progressive central nervous system tumors. Enrollment is recorded as 4, the study status is terminated, and the regimen is described as daily cabozantinib at 40 mg/m2 in 28-day cycles for up to 12 months.

The primary outcome is the number of participants with disease response at 6 months, using lesion-based criteria for complete response, partial response, stable disease, and progressive disease. The registry record does not report the primary outcome count or any analyses. Overall survival and the number of participants with progression free survival are listed as secondary outcomes, but their results are not reported.

Safety entries record 0 participants affected by serious adverse events, 4 affected by other adverse events, and 2 deaths. Event details and treatment relationships are not reported. The record does not state why the study was terminated or provide a statistical analysis plan, missing-data method, or analysis-population definition.